Publications

Google scholar

• 1.

  et al, Z. Y. (2022) Association of Short-term Air Pollution Exposure With SARS-CoV-2 Infection Among Young Adults in Sweden, JAMA Netw Open. 5, e228109.

  AbstractBibTeXEndNoteDOIBibSonomy

  Importance: Mounting ecological evidence shows an association between short-term air pollution exposure and COVID-19, yet no study has examined this association on an individual level. Objective: To estimate the association between short-term exposure to ambient air pollution and SARS-CoV-2 infection among Swedish young adults. Design, setting, and participants: This time-stratified case-crossover study linked the prospective BAMSE (Children, Allergy Milieu, Stockholm, Epidemiology [in Swedish]) birth cohort to the Swedish national infectious disease registry to identify cases with positive results for SARS-CoV-2 polymerase chain reaction (PCR) testing from May 5, 2020, to March 31, 2021. Case day was defined as the date of the PCR test, whereas the dates with the same day of the week within the same calendar month and year were selected as control days. Data analysis was conducted from September 1 to December 31, 2021. Exposures: Daily air pollutant levels (particulate matter with diameter ≤2.5 μm [PM2.5], particulate matter with diameter ≤10 μm [PM10], black carbon [BC], and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion models with high spatiotemporal resolution. Main outcomes and measures: Confirmed SARS-CoV-2 infection among participants within the BAMSE cohort. Distributed-lag models combined with conditional logistic regression models were used to estimate the association. Results: A total of 425 cases were identified, of whom 229 (53.9%) were women, and the median age was 25.6 (IQR, 24.9-26.3) years. The median exposure level for PM2.5 was 4.4 [IQR, 2.6-6.8] μg/m3 on case days; for PM10, 7.7 [IQR, 4.6-11.3] μg/m3 on case days; for BC, 0.3 [IQR, 0.2-0.5] μg/m3 on case days; and for NOx, 8.2 [5.6-14.1] μg/m3 on case days. Median exposure levels on control days were 3.8 [IQR, 2.4-5.9] μg/m3 for PM2.5, 6.6 [IQR, 4.5-10.4] μg/m3 for PM10, 0.2 [IQR, 0.2-0.4] μg/m3 for BC, and 7.7 [IQR, 5.3-12.8] μg/m3 for NOx. Each IQR increase in short-term exposure to PM2.5 on lag 2 was associated with a relative increase in positive results of SARS-CoV-2 PCR testing of 6.8% (95% CI, 2.1%-11.8%); exposure to PM10 on lag 2, 6.9% (95% CI, 2.0%-12.1%); and exposure to BC on lag 1, 5.8% (95% CI, 0.3%-11.6%). These findings were not associated with NOx, nor were they modified by sex, smoking, or having asthma, overweight, or self-reported COVID-19 respiratory symptoms. Conclusions and relevance: The findings of this case-crossover study of Swedish young adults suggest that short-term exposure to particulate matter and BC was associated with increased risk of positive PRC test results for SARS-CoV-2, supporting the broad public health benefits of reducing ambient air pollution levels.

  @article{noauthororeditor,
  abstract = {Importance: Mounting ecological evidence shows an association between short-term air pollution exposure and COVID-19, yet no study has examined this association on an individual level. Objective: To estimate the association between short-term exposure to ambient air pollution and SARS-CoV-2 infection among Swedish young adults. Design, setting, and participants: This time-stratified case-crossover study linked the prospective BAMSE (Children, Allergy Milieu, Stockholm, Epidemiology [in Swedish]) birth cohort to the Swedish national infectious disease registry to identify cases with positive results for SARS-CoV-2 polymerase chain reaction (PCR) testing from May 5, 2020, to March 31, 2021. Case day was defined as the date of the PCR test, whereas the dates with the same day of the week within the same calendar month and year were selected as control days. Data analysis was conducted from September 1 to December 31, 2021. Exposures: Daily air pollutant levels (particulate matter with diameter ≤2.5 μm [PM2.5], particulate matter with diameter ≤10 μm [PM10], black carbon [BC], and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion models with high spatiotemporal resolution. Main outcomes and measures: Confirmed SARS-CoV-2 infection among participants within the BAMSE cohort. Distributed-lag models combined with conditional logistic regression models were used to estimate the association. Results: A total of 425 cases were identified, of whom 229 (53.9%) were women, and the median age was 25.6 (IQR, 24.9-26.3) years. The median exposure level for PM2.5 was 4.4 [IQR, 2.6-6.8] μg/m3 on case days; for PM10, 7.7 [IQR, 4.6-11.3] μg/m3 on case days; for BC, 0.3 [IQR, 0.2-0.5] μg/m3 on case days; and for NOx, 8.2 [5.6-14.1] μg/m3 on case days. Median exposure levels on control days were 3.8 [IQR, 2.4-5.9] μg/m3 for PM2.5, 6.6 [IQR, 4.5-10.4] μg/m3 for PM10, 0.2 [IQR, 0.2-0.4] μg/m3 for BC, and 7.7 [IQR, 5.3-12.8] μg/m3 for NOx. Each IQR increase in short-term exposure to PM2.5 on lag 2 was associated with a relative increase in positive results of SARS-CoV-2 PCR testing of 6.8% (95% CI, 2.1%-11.8%); exposure to PM10 on lag 2, 6.9% (95% CI, 2.0%-12.1%); and exposure to BC on lag 1, 5.8% (95% CI, 0.3%-11.6%). These findings were not associated with NOx, nor were they modified by sex, smoking, or having asthma, overweight, or self-reported COVID-19 respiratory symptoms. Conclusions and relevance: The findings of this case-crossover study of Swedish young adults suggest that short-term exposure to particulate matter and BC was associated with increased risk of positive PRC test results for SARS-CoV-2, supporting the broad public health benefits of reducing ambient air pollution levels.},
  author = {et al, Zhebin Yu},
  journal = {JAMA Netw Open.},
  keywords = 2022,
  number = 4,
  pages = {e228109},
  title = {Association of Short-term Air Pollution Exposure With SARS-CoV-2 Infection Among Young Adults in Sweden},
  volume = 5,
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Zhebin Yu
  %D 2022
  %J JAMA Netw Open.
  %N 4
  %P e228109
  %R 10.1001/jamanetworkopen.2022.8109.
  %T Association of Short-term Air Pollution Exposure With SARS-CoV-2 Infection Among Young Adults in Sweden
  %V 5
  %X Importance: Mounting ecological evidence shows an association between short-term air pollution exposure and COVID-19, yet no study has examined this association on an individual level. Objective: To estimate the association between short-term exposure to ambient air pollution and SARS-CoV-2 infection among Swedish young adults. Design, setting, and participants: This time-stratified case-crossover study linked the prospective BAMSE (Children, Allergy Milieu, Stockholm, Epidemiology [in Swedish]) birth cohort to the Swedish national infectious disease registry to identify cases with positive results for SARS-CoV-2 polymerase chain reaction (PCR) testing from May 5, 2020, to March 31, 2021. Case day was defined as the date of the PCR test, whereas the dates with the same day of the week within the same calendar month and year were selected as control days. Data analysis was conducted from September 1 to December 31, 2021. Exposures: Daily air pollutant levels (particulate matter with diameter ≤2.5 μm [PM2.5], particulate matter with diameter ≤10 μm [PM10], black carbon [BC], and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion models with high spatiotemporal resolution. Main outcomes and measures: Confirmed SARS-CoV-2 infection among participants within the BAMSE cohort. Distributed-lag models combined with conditional logistic regression models were used to estimate the association. Results: A total of 425 cases were identified, of whom 229 (53.9%) were women, and the median age was 25.6 (IQR, 24.9-26.3) years. The median exposure level for PM2.5 was 4.4 [IQR, 2.6-6.8] μg/m3 on case days; for PM10, 7.7 [IQR, 4.6-11.3] μg/m3 on case days; for BC, 0.3 [IQR, 0.2-0.5] μg/m3 on case days; and for NOx, 8.2 [5.6-14.1] μg/m3 on case days. Median exposure levels on control days were 3.8 [IQR, 2.4-5.9] μg/m3 for PM2.5, 6.6 [IQR, 4.5-10.4] μg/m3 for PM10, 0.2 [IQR, 0.2-0.4] μg/m3 for BC, and 7.7 [IQR, 5.3-12.8] μg/m3 for NOx. Each IQR increase in short-term exposure to PM2.5 on lag 2 was associated with a relative increase in positive results of SARS-CoV-2 PCR testing of 6.8% (95% CI, 2.1%-11.8%); exposure to PM10 on lag 2, 6.9% (95% CI, 2.0%-12.1%); and exposure to BC on lag 1, 5.8% (95% CI, 0.3%-11.6%). These findings were not associated with NOx, nor were they modified by sex, smoking, or having asthma, overweight, or self-reported COVID-19 respiratory symptoms. Conclusions and relevance: The findings of this case-crossover study of Swedish young adults suggest that short-term exposure to particulate matter and BC was associated with increased risk of positive PRC test results for SARS-CoV-2, supporting the broad public health benefits of reducing ambient air pollution levels.
  

• 1.

  et al, J. A. S. (2022) Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus, Genes Immun..

  AbstractURLBibTeXEndNoteDOIBibSonomy

  The Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections. Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. However, potential mechanisms contributing to these associations have not yet been defined. Here, we used transcriptomic and genomic data from the Milieu Interieur cohort of 1000 healthy individuals to explore the effect of Rhesus status on the immune response. We used the rs590787 SNP in the RHD gene to classify the 1000 donors as either RhD-positive or -negative. Whole blood was stimulated with LPS, polyIC, and the live influenza A virus and the NanoString human immunology panel of 560 genes used to assess donor immune response and to investigate sex-specific effects. Using regression analysis, we observed no significant differences in responses to polyIC or LPS between RhD-positive and -negative individuals. However, upon sex-specific analysis, we observed over 40 differentially expressed genes (DEGs) between RhD-positive (n = 384) and RhD-negative males (n = 75) after influenza virus stimulation. Interestingly these Rhesus-associated differences were not seen in females. Further investigation, using gene set enrichment analysis, revealed enhanced IFNγ signalling in RhD-negative males. This amplified IFNγ signalling axis may explain the increased viral resistance previously described in RhD-negative individuals.

  @article{noauthororeditor,
  abstract = {The Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections. Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. However, potential mechanisms contributing to these associations have not yet been defined. Here, we used transcriptomic and genomic data from the Milieu Interieur cohort of 1000 healthy individuals to explore the effect of Rhesus status on the immune response. We used the rs590787 SNP in the RHD gene to classify the 1000 donors as either RhD-positive or -negative. Whole blood was stimulated with LPS, polyIC, and the live influenza A virus and the NanoString human immunology panel of 560 genes used to assess donor immune response and to investigate sex-specific effects. Using regression analysis, we observed no significant differences in responses to polyIC or LPS between RhD-positive and -negative individuals. However, upon sex-specific analysis, we observed over 40 differentially expressed genes (DEGs) between RhD-positive (n = 384) and RhD-negative males (n = 75) after influenza virus stimulation. Interestingly these Rhesus-associated differences were not seen in females. Further investigation, using gene set enrichment analysis, revealed enhanced IFNγ signalling in RhD-negative males. This amplified IFNγ signalling axis may explain the increased viral resistance previously described in RhD-negative individuals.},
  author = {et al, Jamie A Sugrue},
  journal = {Genes Immun.},
  keywords = {Influenza},
  title = {Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus},
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Jamie A Sugrue
  %D 2022
  %J Genes Immun.
  %R 10.1038/s41435-022-00169-5
  %T Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus
  %U /brokenurl#10.1038/s41435-022-00169-5
  %X The Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections. Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. However, potential mechanisms contributing to these associations have not yet been defined. Here, we used transcriptomic and genomic data from the Milieu Interieur cohort of 1000 healthy individuals to explore the effect of Rhesus status on the immune response. We used the rs590787 SNP in the RHD gene to classify the 1000 donors as either RhD-positive or -negative. Whole blood was stimulated with LPS, polyIC, and the live influenza A virus and the NanoString human immunology panel of 560 genes used to assess donor immune response and to investigate sex-specific effects. Using regression analysis, we observed no significant differences in responses to polyIC or LPS between RhD-positive and -negative individuals. However, upon sex-specific analysis, we observed over 40 differentially expressed genes (DEGs) between RhD-positive (n = 384) and RhD-negative males (n = 75) after influenza virus stimulation. Interestingly these Rhesus-associated differences were not seen in females. Further investigation, using gene set enrichment analysis, revealed enhanced IFNγ signalling in RhD-negative males. This amplified IFNγ signalling axis may explain the increased viral resistance previously described in RhD-negative individuals.
  

• 1.

  et al, T. (2022) Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency, J Exp Med. 219, e20220202.

  AbstractBibTeXEndNoteDOIBibSonomy

  Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients' fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2-specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.

  @article{noauthororeditor,
  abstract = {Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients' fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2-specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.},
  author = {et al, Tessa},
  journal = {J Exp Med.},
  keywords = {IRF7 deficiency},
  month = {July 4},
  number = 7,
  pages = {e20220202},
  title = {Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency},
  volume = 219,
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Tessa
  %D 2022
  %J J Exp Med.
  %N 7
  %P e20220202
  %R 10.1084/jem.20220202
  %T Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency
  %V 219
  %X Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients' fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2-specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.
  

• 1.

  Brodin, P. (2022) SARS-CoV-2 infections in children: understanding diverse outcomes, Immunity, Elsevier.

  URLBibTeXEndNoteDOIBibSonomy

  @article{brodinsarscov2,
  author = {Brodin, Petter},
  booktitle = {Immunity},
  journal = {Immunity},
  keywords = {covid-19},
  publisher = {Elsevier},
  title = {SARS-CoV-2 infections in children: understanding diverse outcomes},
  year = 2022
  }
  

  %0 Journal Article
  %1 brodinsarscov2
  %A Brodin, Petter
  %B Immunity
  %D 2022
  %I Elsevier
  %J Immunity
  %R 10.1016/j.immuni.2022.01.014
  %T SARS-CoV-2 infections in children: understanding diverse outcomes
  %U https://doi.org/10.1016/j.immuni.2022.01.014
  

• 1.

  Taeschler, P., Cervia, C., Zurbuchen, Y., Hasler, S., Pou, C., Tan, Z., Adamo, S., Raeber, M. E., Bächli, E., Rudiger, A., Stüssi-Helbling, M., Huber, L. C., Brodin, P., Nilsson, J., Probst-Müller, E., and Boyman, O. (2022) Autoantibodies in COVID-19 correlate with anti-viral humoral responses and distinct immune signatures, Cold Spring Harbor Laboratory.

  URLBibTeXEndNoteDOIBibSonomy

  @article{Taeschler_2022,
  author = {Taeschler, Patrick and Cervia, Carlo and Zurbuchen, Yves and Hasler, Sara and Pou, Christian and Tan, Ziyang and Adamo, Sarah and Raeber, Miro E. and Bächli, Esther and Rudiger, Alain and Stüssi-Helbling, Melina and Huber, Lars C. and Brodin, Petter and Nilsson, Jakob and Probst-Müller, Elsbeth and Boyman, Onur},
  keywords = {covid-19},
  month = {jan},
  publisher = {Cold Spring Harbor Laboratory},
  title = {Autoantibodies in COVID-19 correlate with anti-viral humoral responses and distinct immune signatures},
  year = 2022
  }
  

  %0 Journal Article
  %1 Taeschler_2022
  %A Taeschler, Patrick
  %A Cervia, Carlo
  %A Zurbuchen, Yves
  %A Hasler, Sara
  %A Pou, Christian
  %A Tan, Ziyang
  %A Adamo, Sarah
  %A Raeber, Miro E.
  %A Bächli, Esther
  %A Rudiger, Alain
  %A Stüssi-Helbling, Melina
  %A Huber, Lars C.
  %A Brodin, Petter
  %A Nilsson, Jakob
  %A Probst-Müller, Elsbeth
  %A Boyman, Onur
  %D 2022
  %I Cold Spring Harbor Laboratory
  %R 10.1101/2022.01.08.22268901
  %T Autoantibodies in COVID-19 correlate with anti-viral humoral responses and distinct immune signatures
  %U https://doi.org/10.1101%2F2022.01.08.22268901
  

• 1.

  et al, Z. (2022) Human genetic and immunological determinants of critical COVID-19 pneumonia, Nature.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  SARS-CoV-2 infection is benign in most individuals but, in ˜10% of cases, it triggers hypoxemic COVID-19 pneumonia, which becomes critical in ˜3% of cases. The ensuing risk of death (˜1%) doubles every five years from childhood onward and is ˜1.5 times greater in men than in women. What are the molecular and cellular determinants of critical COVID-19 pneumonia? Inborn errors of type I IFNs, including autosomal TLR3 and X-linked TLR7 deficiencies, are found in ˜1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing autoantibodies neutralizing IFN-α, -β, and/or -ω, which are more common in men than in women, are found in ˜15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can apparently be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defense against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation.

  @article{noauthororeditor,
  abstract = {SARS-CoV-2 infection is benign in most individuals but, in ˜10% of cases, it triggers hypoxemic COVID-19 pneumonia, which becomes critical in ˜3% of cases. The ensuing risk of death (˜1%) doubles every five years from childhood onward and is ˜1.5 times greater in men than in women. What are the molecular and cellular determinants of critical COVID-19 pneumonia? Inborn errors of type I IFNs, including autosomal TLR3 and X-linked TLR7 deficiencies, are found in ˜1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing autoantibodies neutralizing IFN-α, -β, and/or -ω, which are more common in men than in women, are found in ˜15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can apparently be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defense against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation.},
  author = {et al, Zhang},
  journal = {Nature},
  keywords = {covid-19},
  title = {Human genetic and immunological determinants of critical COVID-19 pneumonia},
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Zhang
  %D 2022
  %J Nature
  %R 10.1038/s41586-022-04447-0
  %T Human genetic and immunological determinants of critical COVID-19 pneumonia
  %U /brokenurl#10.1038/s41586-022-04447-0
  %X SARS-CoV-2 infection is benign in most individuals but, in ˜10% of cases, it triggers hypoxemic COVID-19 pneumonia, which becomes critical in ˜3% of cases. The ensuing risk of death (˜1%) doubles every five years from childhood onward and is ˜1.5 times greater in men than in women. What are the molecular and cellular determinants of critical COVID-19 pneumonia? Inborn errors of type I IFNs, including autosomal TLR3 and X-linked TLR7 deficiencies, are found in ˜1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing autoantibodies neutralizing IFN-α, -β, and/or -ω, which are more common in men than in women, are found in ˜15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can apparently be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defense against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation.
  

• 1.

  et al, O. (2022) Longitudinal analyses of development of the immune system during the first five years of life in relation to lifestyle, Allergy.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Background: Changes in immune cell composition during the immunological window within the first years after birth are not fully understood, especially the effect that different lifestyles might have on immune cell functionality. Methods: Peripheral blood mononuclear cells from mothers and their children at birth and at two and five years were analyzed by mass cytometry. Immune cell composition and functionality was analyzed according to family lifestyle (anthroposophic and non-anthroposophic). Results: We found no significant differences in the proportions of major immune lineages between anthroposophic and non-anthroposophic children at each timepoint, but there were clear changes over time in the proportions of mononuclear leukocytes, especially in B cells and T lymphocytes. Phenotypic distances between cord blood and maternal blood were high at birth but decreased sharply the first two years, indicating strong phenotypic convergence with maternal cells. We found that children exhibited similar stimulation responses at birth, but subsequently segregated into two discrete functional trajectories. Trajectory 1 was associated with a decrease in tumor necrosis factor alpha (TNFa) production by CD4+ T- and NK-cells, while Trajectory 2 depicted an increase in the production of IL-2 and interferon gamma (INFg) by T-cells. In both trajectories there was an increase in IL-17A production by T-cells resulting in prominent differences at five years of age. Conclusions: This exploratory study suggest that leukocyte frequencies and cell phenotypes change with age in the same way across all children, while functional development follow one of two discrete trajectories that largely segregate by family lifestyle, supporting the hypothesis that early environmental exposures imprint immune cell function which may contribute to IgE sensitization. Our results also support that the first two years are critical for the environmental exposures to imprint the immune cells. Further studies with larger sample sizes are required to validate our findings. Keywords: Anthroposophic lifestyle; IgE sensitization to allergens; PBMC; cytokine production; mass cytometry.

  @article{noauthororeditor,
  abstract = {Background: Changes in immune cell composition during the immunological window within the first years after birth are not fully understood, especially the effect that different lifestyles might have on immune cell functionality. Methods: Peripheral blood mononuclear cells from mothers and their children at birth and at two and five years were analyzed by mass cytometry. Immune cell composition and functionality was analyzed according to family lifestyle (anthroposophic and non-anthroposophic). Results: We found no significant differences in the proportions of major immune lineages between anthroposophic and non-anthroposophic children at each timepoint, but there were clear changes over time in the proportions of mononuclear leukocytes, especially in B cells and T lymphocytes. Phenotypic distances between cord blood and maternal blood were high at birth but decreased sharply the first two years, indicating strong phenotypic convergence with maternal cells. We found that children exhibited similar stimulation responses at birth, but subsequently segregated into two discrete functional trajectories. Trajectory 1 was associated with a decrease in tumor necrosis factor alpha (TNFa) production by CD4+ T- and NK-cells, while Trajectory 2 depicted an increase in the production of IL-2 and interferon gamma (INFg) by T-cells. In both trajectories there was an increase in IL-17A production by T-cells resulting in prominent differences at five years of age. Conclusions: This exploratory study suggest that leukocyte frequencies and cell phenotypes change with age in the same way across all children, while functional development follow one of two discrete trajectories that largely segregate by family lifestyle, supporting the hypothesis that early environmental exposures imprint immune cell function which may contribute to IgE sensitization. Our results also support that the first two years are critical for the environmental exposures to imprint the immune cells. Further studies with larger sample sizes are required to validate our findings. Keywords: Anthroposophic lifestyle; IgE sensitization to allergens; PBMC; cytokine production; mass cytometry.},
  author = {et al, Olin},
  journal = {Allergy},
  keywords = {Birth lifestyle},
  title = {Longitudinal analyses of development of the immune system during the first five years of life in relation to lifestyle},
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Olin
  %D 2022
  %J Allergy
  %R 10.1111/all.15232
  %T Longitudinal analyses of development of the immune system during the first five years of life in relation to lifestyle
  %U /brokenurl#10.1111/all.15232
  %X Background: Changes in immune cell composition during the immunological window within the first years after birth are not fully understood, especially the effect that different lifestyles might have on immune cell functionality. Methods: Peripheral blood mononuclear cells from mothers and their children at birth and at two and five years were analyzed by mass cytometry. Immune cell composition and functionality was analyzed according to family lifestyle (anthroposophic and non-anthroposophic). Results: We found no significant differences in the proportions of major immune lineages between anthroposophic and non-anthroposophic children at each timepoint, but there were clear changes over time in the proportions of mononuclear leukocytes, especially in B cells and T lymphocytes. Phenotypic distances between cord blood and maternal blood were high at birth but decreased sharply the first two years, indicating strong phenotypic convergence with maternal cells. We found that children exhibited similar stimulation responses at birth, but subsequently segregated into two discrete functional trajectories. Trajectory 1 was associated with a decrease in tumor necrosis factor alpha (TNFa) production by CD4+ T- and NK-cells, while Trajectory 2 depicted an increase in the production of IL-2 and interferon gamma (INFg) by T-cells. In both trajectories there was an increase in IL-17A production by T-cells resulting in prominent differences at five years of age. Conclusions: This exploratory study suggest that leukocyte frequencies and cell phenotypes change with age in the same way across all children, while functional development follow one of two discrete trajectories that largely segregate by family lifestyle, supporting the hypothesis that early environmental exposures imprint immune cell function which may contribute to IgE sensitization. Our results also support that the first two years are critical for the environmental exposures to imprint the immune cells. Further studies with larger sample sizes are required to validate our findings. Keywords: Anthroposophic lifestyle; IgE sensitization to allergens; PBMC; cytokine production; mass cytometry.
  

• 1.

  Brodin, P. et al. (2022) Studying severe long COVID to understand post-infectious disorders beyond COVID-19, Nature Medicine.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Brodin, P et al},
  journal = {Nature Medicine},
  keywords = {COVID},
  title = {Studying severe long COVID to understand post-infectious disorders beyond COVID-19},
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Brodin, P et al
  %D 2022
  %J Nature Medicine
  %R https://doi.org/10.1038/s41591-022-01766-7
  %T Studying severe long COVID to understand post-infectious disorders beyond COVID-19
  

• 1.

  et al, Z. Y. (2022) Association of Short-term Air Pollution Exposure With SARS-CoV-2 Infection Among Young Adults in Sweden, JAMA Netw Open.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Importance: Mounting ecological evidence shows an association between short-term air pollution exposure and COVID-19, yet no study has examined this association on an individual level. Objective: To estimate the association between short-term exposure to ambient air pollution and SARS-CoV-2 infection among Swedish young adults. Design, setting, and participants: This time-stratified case-crossover study linked the prospective BAMSE (Children, Allergy Milieu, Stockholm, Epidemiology [in Swedish]) birth cohort to the Swedish national infectious disease registry to identify cases with positive results for SARS-CoV-2 polymerase chain reaction (PCR) testing from May 5, 2020, to March 31, 2021. Case day was defined as the date of the PCR test, whereas the dates with the same day of the week within the same calendar month and year were selected as control days. Data analysis was conducted from September 1 to December 31, 2021. Exposures: Daily air pollutant levels (particulate matter with diameter ≤2.5 μm [PM2.5], particulate matter with diameter ≤10 μm [PM10], black carbon [BC], and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion models with high spatiotemporal resolution. Main outcomes and measures: Confirmed SARS-CoV-2 infection among participants within the BAMSE cohort. Distributed-lag models combined with conditional logistic regression models were used to estimate the association. Results: A total of 425 cases were identified, of whom 229 (53.9%) were women, and the median age was 25.6 (IQR, 24.9-26.3) years. The median exposure level for PM2.5 was 4.4 [IQR, 2.6-6.8] μg/m3 on case days; for PM10, 7.7 [IQR, 4.6-11.3] μg/m3 on case days; for BC, 0.3 [IQR, 0.2-0.5] μg/m3 on case days; and for NOx, 8.2 [5.6-14.1] μg/m3 on case days. Median exposure levels on control days were 3.8 [IQR, 2.4-5.9] μg/m3 for PM2.5, 6.6 [IQR, 4.5-10.4] μg/m3 for PM10, 0.2 [IQR, 0.2-0.4] μg/m3 for BC, and 7.7 [IQR, 5.3-12.8] μg/m3 for NOx. Each IQR increase in short-term exposure to PM2.5 on lag 2 was associated with a relative increase in positive results of SARS-CoV-2 PCR testing of 6.8% (95% CI, 2.1%-11.8%); exposure to PM10 on lag 2, 6.9% (95% CI, 2.0%-12.1%); and exposure to BC on lag 1, 5.8% (95% CI, 0.3%-11.6%). These findings were not associated with NOx, nor were they modified by sex, smoking, or having asthma, overweight, or self-reported COVID-19 respiratory symptoms. Conclusions and relevance: The findings of this case-crossover study of Swedish young adults suggest that short-term exposure to particulate matter and BC was associated with increased risk of positive PRC test results for SARS-CoV-2, supporting the broad public health benefits of reducing ambient air pollution levels.

  @article{noauthororeditor,
  abstract = {Importance: Mounting ecological evidence shows an association between short-term air pollution exposure and COVID-19, yet no study has examined this association on an individual level. Objective: To estimate the association between short-term exposure to ambient air pollution and SARS-CoV-2 infection among Swedish young adults. Design, setting, and participants: This time-stratified case-crossover study linked the prospective BAMSE (Children, Allergy Milieu, Stockholm, Epidemiology [in Swedish]) birth cohort to the Swedish national infectious disease registry to identify cases with positive results for SARS-CoV-2 polymerase chain reaction (PCR) testing from May 5, 2020, to March 31, 2021. Case day was defined as the date of the PCR test, whereas the dates with the same day of the week within the same calendar month and year were selected as control days. Data analysis was conducted from September 1 to December 31, 2021. Exposures: Daily air pollutant levels (particulate matter with diameter ≤2.5 μm [PM2.5], particulate matter with diameter ≤10 μm [PM10], black carbon [BC], and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion models with high spatiotemporal resolution. Main outcomes and measures: Confirmed SARS-CoV-2 infection among participants within the BAMSE cohort. Distributed-lag models combined with conditional logistic regression models were used to estimate the association. Results: A total of 425 cases were identified, of whom 229 (53.9%) were women, and the median age was 25.6 (IQR, 24.9-26.3) years. The median exposure level for PM2.5 was 4.4 [IQR, 2.6-6.8] μg/m3 on case days; for PM10, 7.7 [IQR, 4.6-11.3] μg/m3 on case days; for BC, 0.3 [IQR, 0.2-0.5] μg/m3 on case days; and for NOx, 8.2 [5.6-14.1] μg/m3 on case days. Median exposure levels on control days were 3.8 [IQR, 2.4-5.9] μg/m3 for PM2.5, 6.6 [IQR, 4.5-10.4] μg/m3 for PM10, 0.2 [IQR, 0.2-0.4] μg/m3 for BC, and 7.7 [IQR, 5.3-12.8] μg/m3 for NOx. Each IQR increase in short-term exposure to PM2.5 on lag 2 was associated with a relative increase in positive results of SARS-CoV-2 PCR testing of 6.8% (95% CI, 2.1%-11.8%); exposure to PM10 on lag 2, 6.9% (95% CI, 2.0%-12.1%); and exposure to BC on lag 1, 5.8% (95% CI, 0.3%-11.6%). These findings were not associated with NOx, nor were they modified by sex, smoking, or having asthma, overweight, or self-reported COVID-19 respiratory symptoms. Conclusions and relevance: The findings of this case-crossover study of Swedish young adults suggest that short-term exposure to particulate matter and BC was associated with increased risk of positive PRC test results for SARS-CoV-2, supporting the broad public health benefits of reducing ambient air pollution levels.},
  author = {et al, Zhebin Yu},
  journal = {JAMA Netw Open},
  keywords = {SARS-Cov-2},
  title = {Association of Short-term Air Pollution Exposure With SARS-CoV-2 Infection Among Young Adults in Sweden},
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Zhebin Yu
  %D 2022
  %J JAMA Netw Open
  %R 10.1001/jamanetworkopen.2022.8109.
  %T Association of Short-term Air Pollution Exposure With SARS-CoV-2 Infection Among Young Adults in Sweden
  %U /brokenurl#10.1001/jamanetworkopen.2022.8109.
  %X Importance: Mounting ecological evidence shows an association between short-term air pollution exposure and COVID-19, yet no study has examined this association on an individual level. Objective: To estimate the association between short-term exposure to ambient air pollution and SARS-CoV-2 infection among Swedish young adults. Design, setting, and participants: This time-stratified case-crossover study linked the prospective BAMSE (Children, Allergy Milieu, Stockholm, Epidemiology [in Swedish]) birth cohort to the Swedish national infectious disease registry to identify cases with positive results for SARS-CoV-2 polymerase chain reaction (PCR) testing from May 5, 2020, to March 31, 2021. Case day was defined as the date of the PCR test, whereas the dates with the same day of the week within the same calendar month and year were selected as control days. Data analysis was conducted from September 1 to December 31, 2021. Exposures: Daily air pollutant levels (particulate matter with diameter ≤2.5 μm [PM2.5], particulate matter with diameter ≤10 μm [PM10], black carbon [BC], and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion models with high spatiotemporal resolution. Main outcomes and measures: Confirmed SARS-CoV-2 infection among participants within the BAMSE cohort. Distributed-lag models combined with conditional logistic regression models were used to estimate the association. Results: A total of 425 cases were identified, of whom 229 (53.9%) were women, and the median age was 25.6 (IQR, 24.9-26.3) years. The median exposure level for PM2.5 was 4.4 [IQR, 2.6-6.8] μg/m3 on case days; for PM10, 7.7 [IQR, 4.6-11.3] μg/m3 on case days; for BC, 0.3 [IQR, 0.2-0.5] μg/m3 on case days; and for NOx, 8.2 [5.6-14.1] μg/m3 on case days. Median exposure levels on control days were 3.8 [IQR, 2.4-5.9] μg/m3 for PM2.5, 6.6 [IQR, 4.5-10.4] μg/m3 for PM10, 0.2 [IQR, 0.2-0.4] μg/m3 for BC, and 7.7 [IQR, 5.3-12.8] μg/m3 for NOx. Each IQR increase in short-term exposure to PM2.5 on lag 2 was associated with a relative increase in positive results of SARS-CoV-2 PCR testing of 6.8% (95% CI, 2.1%-11.8%); exposure to PM10 on lag 2, 6.9% (95% CI, 2.0%-12.1%); and exposure to BC on lag 1, 5.8% (95% CI, 0.3%-11.6%). These findings were not associated with NOx, nor were they modified by sex, smoking, or having asthma, overweight, or self-reported COVID-19 respiratory symptoms. Conclusions and relevance: The findings of this case-crossover study of Swedish young adults suggest that short-term exposure to particulate matter and BC was associated with increased risk of positive PRC test results for SARS-CoV-2, supporting the broad public health benefits of reducing ambient air pollution levels.
  

• 1.

  et al, C. (2022) Integrative genetic and immune cell analysis of plasma proteins in healthy donors identifies novel associations involving primary immune deficiency genes, Genome Med. 14.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Background: Blood plasma proteins play an important role in immune defense against pathogens, including cytokine signaling, the complement system, and the acute-phase response. Recent large-scale studies have reported genetic (i.e., protein quantitative trait loci, pQTLs) and non-genetic factors, such as age and sex, as major determinants to inter-individual variability in immune response variation. However, the contribution of blood-cell composition to plasma protein heterogeneity has not been fully characterized and may act as a mediating factor in association studies. Methods: Here, we evaluated plasma protein levels from 400 unrelated healthy individuals of western European ancestry, who were stratified by sex and two decades of life (20-29 and 60-69 years), from the Milieu Intérieur cohort. We quantified 229 proteins by Luminex in a clinically certified laboratory and their levels of variation were analyzed together with 5.2 million single-nucleotide polymorphisms. With respect to non-genetic variables, we included 254 lifestyle and biochemical factors, as well as counts of seven circulating immune cell populations measured by hemogram and standardized flow cytometry. Results: Collectively, we found 152 significant associations involving 49 proteins and 20 non-genetic variables. Consistent with previous studies, age and sex showed a global, pervasive impact on plasma protein heterogeneity, while body mass index and other health status variables were among the non-genetic factors with the highest number of associations. After controlling for these covariates, we identified 100 and 12 pQTLs acting in cis and trans, respectively, collectively associated with 87 plasma proteins and including 19 novel genetic associations. Genetic factors explained the largest fraction of the variability of plasma protein levels, as compared to non-genetic factors. In addition, blood-cell fractions, including leukocytes, lymphocytes, monocytes, neutrophils, eosinophils, basophils, and platelets, had a larger contribution to inter-individual variability than age and sex and appeared as confounders of specific genetic associations. Finally, we identified new genetic associations with plasma protein levels of five monogenic Mendelian disease genes including two primary immunodeficiency genes (Ficolin-3 and FAS). Conclusions: Our study identified novel genetic and non-genetic factors associated to plasma protein levels which may inform health status and disease management. Keywords: Immune cells; Immune variability; Plasma proteins; pQTL.

  @article{noauthororeditor,
  abstract = {Background: Blood plasma proteins play an important role in immune defense against pathogens, including cytokine signaling, the complement system, and the acute-phase response. Recent large-scale studies have reported genetic (i.e., protein quantitative trait loci, pQTLs) and non-genetic factors, such as age and sex, as major determinants to inter-individual variability in immune response variation. However, the contribution of blood-cell composition to plasma protein heterogeneity has not been fully characterized and may act as a mediating factor in association studies. Methods: Here, we evaluated plasma protein levels from 400 unrelated healthy individuals of western European ancestry, who were stratified by sex and two decades of life (20-29 and 60-69 years), from the Milieu Intérieur cohort. We quantified 229 proteins by Luminex in a clinically certified laboratory and their levels of variation were analyzed together with 5.2 million single-nucleotide polymorphisms. With respect to non-genetic variables, we included 254 lifestyle and biochemical factors, as well as counts of seven circulating immune cell populations measured by hemogram and standardized flow cytometry. Results: Collectively, we found 152 significant associations involving 49 proteins and 20 non-genetic variables. Consistent with previous studies, age and sex showed a global, pervasive impact on plasma protein heterogeneity, while body mass index and other health status variables were among the non-genetic factors with the highest number of associations. After controlling for these covariates, we identified 100 and 12 pQTLs acting in cis and trans, respectively, collectively associated with 87 plasma proteins and including 19 novel genetic associations. Genetic factors explained the largest fraction of the variability of plasma protein levels, as compared to non-genetic factors. In addition, blood-cell fractions, including leukocytes, lymphocytes, monocytes, neutrophils, eosinophils, basophils, and platelets, had a larger contribution to inter-individual variability than age and sex and appeared as confounders of specific genetic associations. Finally, we identified new genetic associations with plasma protein levels of five monogenic Mendelian disease genes including two primary immunodeficiency genes (Ficolin-3 and FAS). Conclusions: Our study identified novel genetic and non-genetic factors associated to plasma protein levels which may inform health status and disease management. Keywords: Immune cells; Immune variability; Plasma proteins; pQTL.},
  author = {et al, Caron},
  journal = {Genome Med.},
  keywords = {PID},
  number = 1,
  title = {Integrative genetic and immune cell analysis of plasma proteins in healthy donors identifies novel associations involving primary immune deficiency genes},
  volume = 14,
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Caron
  %D 2022
  %J Genome Med.
  %N 1
  %R 10.1186/s13073-022-01032-y
  %T Integrative genetic and immune cell analysis of plasma proteins in healthy donors identifies novel associations involving primary immune deficiency genes
  %U /brokenurl#10.1186/s13073-022-01032-y
  %V 14
  %X Background: Blood plasma proteins play an important role in immune defense against pathogens, including cytokine signaling, the complement system, and the acute-phase response. Recent large-scale studies have reported genetic (i.e., protein quantitative trait loci, pQTLs) and non-genetic factors, such as age and sex, as major determinants to inter-individual variability in immune response variation. However, the contribution of blood-cell composition to plasma protein heterogeneity has not been fully characterized and may act as a mediating factor in association studies. Methods: Here, we evaluated plasma protein levels from 400 unrelated healthy individuals of western European ancestry, who were stratified by sex and two decades of life (20-29 and 60-69 years), from the Milieu Intérieur cohort. We quantified 229 proteins by Luminex in a clinically certified laboratory and their levels of variation were analyzed together with 5.2 million single-nucleotide polymorphisms. With respect to non-genetic variables, we included 254 lifestyle and biochemical factors, as well as counts of seven circulating immune cell populations measured by hemogram and standardized flow cytometry. Results: Collectively, we found 152 significant associations involving 49 proteins and 20 non-genetic variables. Consistent with previous studies, age and sex showed a global, pervasive impact on plasma protein heterogeneity, while body mass index and other health status variables were among the non-genetic factors with the highest number of associations. After controlling for these covariates, we identified 100 and 12 pQTLs acting in cis and trans, respectively, collectively associated with 87 plasma proteins and including 19 novel genetic associations. Genetic factors explained the largest fraction of the variability of plasma protein levels, as compared to non-genetic factors. In addition, blood-cell fractions, including leukocytes, lymphocytes, monocytes, neutrophils, eosinophils, basophils, and platelets, had a larger contribution to inter-individual variability than age and sex and appeared as confounders of specific genetic associations. Finally, we identified new genetic associations with plasma protein levels of five monogenic Mendelian disease genes including two primary immunodeficiency genes (Ficolin-3 and FAS). Conclusions: Our study identified novel genetic and non-genetic factors associated to plasma protein levels which may inform health status and disease management. Keywords: Immune cells; Immune variability; Plasma proteins; pQTL.
  

• 1.

  et al, Z. Y. (2022) Association of Short-term Air Pollution Exposure With SARS-CoV-2 Infection Among Young Adults in Sweden, JAMA Netw Open..

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Importance: Mounting ecological evidence shows an association between short-term air pollution exposure and COVID-19, yet no study has examined this association on an individual level. Objective: To estimate the association between short-term exposure to ambient air pollution and SARS-CoV-2 infection among Swedish young adults. Design, setting, and participants: This time-stratified case-crossover study linked the prospective BAMSE (Children, Allergy Milieu, Stockholm, Epidemiology [in Swedish]) birth cohort to the Swedish national infectious disease registry to identify cases with positive results for SARS-CoV-2 polymerase chain reaction (PCR) testing from May 5, 2020, to March 31, 2021. Case day was defined as the date of the PCR test, whereas the dates with the same day of the week within the same calendar month and year were selected as control days. Data analysis was conducted from September 1 to December 31, 2021. Exposures: Daily air pollutant levels (particulate matter with diameter ≤2.5 μm [PM2.5], particulate matter with diameter ≤10 μm [PM10], black carbon [BC], and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion models with high spatiotemporal resolution. Main outcomes and measures: Confirmed SARS-CoV-2 infection among participants within the BAMSE cohort. Distributed-lag models combined with conditional logistic regression models were used to estimate the association. Results: A total of 425 cases were identified, of whom 229 (53.9%) were women, and the median age was 25.6 (IQR, 24.9-26.3) years. The median exposure level for PM2.5 was 4.4 [IQR, 2.6-6.8] μg/m3 on case days; for PM10, 7.7 [IQR, 4.6-11.3] μg/m3 on case days; for BC, 0.3 [IQR, 0.2-0.5] μg/m3 on case days; and for NOx, 8.2 [5.6-14.1] μg/m3 on case days. Median exposure levels on control days were 3.8 [IQR, 2.4-5.9] μg/m3 for PM2.5, 6.6 [IQR, 4.5-10.4] μg/m3 for PM10, 0.2 [IQR, 0.2-0.4] μg/m3 for BC, and 7.7 [IQR, 5.3-12.8] μg/m3 for NOx. Each IQR increase in short-term exposure to PM2.5 on lag 2 was associated with a relative increase in positive results of SARS-CoV-2 PCR testing of 6.8% (95% CI, 2.1%-11.8%); exposure to PM10 on lag 2, 6.9% (95% CI, 2.0%-12.1%); and exposure to BC on lag 1, 5.8% (95% CI, 0.3%-11.6%). These findings were not associated with NOx, nor were they modified by sex, smoking, or having asthma, overweight, or self-reported COVID-19 respiratory symptoms. Conclusions and relevance: The findings of this case-crossover study of Swedish young adults suggest that short-term exposure to particulate matter and BC was associated with increased risk of positive PRC test results for SARS-CoV-2, supporting the broad public health benefits of reducing ambient air pollution levels.

  @article{noauthororeditor,
  abstract = {Importance: Mounting ecological evidence shows an association between short-term air pollution exposure and COVID-19, yet no study has examined this association on an individual level. Objective: To estimate the association between short-term exposure to ambient air pollution and SARS-CoV-2 infection among Swedish young adults. Design, setting, and participants: This time-stratified case-crossover study linked the prospective BAMSE (Children, Allergy Milieu, Stockholm, Epidemiology [in Swedish]) birth cohort to the Swedish national infectious disease registry to identify cases with positive results for SARS-CoV-2 polymerase chain reaction (PCR) testing from May 5, 2020, to March 31, 2021. Case day was defined as the date of the PCR test, whereas the dates with the same day of the week within the same calendar month and year were selected as control days. Data analysis was conducted from September 1 to December 31, 2021. Exposures: Daily air pollutant levels (particulate matter with diameter ≤2.5 μm [PM2.5], particulate matter with diameter ≤10 μm [PM10], black carbon [BC], and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion models with high spatiotemporal resolution. Main outcomes and measures: Confirmed SARS-CoV-2 infection among participants within the BAMSE cohort. Distributed-lag models combined with conditional logistic regression models were used to estimate the association. Results: A total of 425 cases were identified, of whom 229 (53.9%) were women, and the median age was 25.6 (IQR, 24.9-26.3) years. The median exposure level for PM2.5 was 4.4 [IQR, 2.6-6.8] μg/m3 on case days; for PM10, 7.7 [IQR, 4.6-11.3] μg/m3 on case days; for BC, 0.3 [IQR, 0.2-0.5] μg/m3 on case days; and for NOx, 8.2 [5.6-14.1] μg/m3 on case days. Median exposure levels on control days were 3.8 [IQR, 2.4-5.9] μg/m3 for PM2.5, 6.6 [IQR, 4.5-10.4] μg/m3 for PM10, 0.2 [IQR, 0.2-0.4] μg/m3 for BC, and 7.7 [IQR, 5.3-12.8] μg/m3 for NOx. Each IQR increase in short-term exposure to PM2.5 on lag 2 was associated with a relative increase in positive results of SARS-CoV-2 PCR testing of 6.8% (95% CI, 2.1%-11.8%); exposure to PM10 on lag 2, 6.9% (95% CI, 2.0%-12.1%); and exposure to BC on lag 1, 5.8% (95% CI, 0.3%-11.6%). These findings were not associated with NOx, nor were they modified by sex, smoking, or having asthma, overweight, or self-reported COVID-19 respiratory symptoms. Conclusions and relevance: The findings of this case-crossover study of Swedish young adults suggest that short-term exposure to particulate matter and BC was associated with increased risk of positive PRC test results for SARS-CoV-2, supporting the broad public health benefits of reducing ambient air pollution levels.},
  author = {et al, Zhebin Yu},
  journal = {JAMA Netw Open.},
  keywords = {SARS-CoV-2},
  title = {Association of Short-term Air Pollution Exposure With SARS-CoV-2 Infection Among Young Adults in Sweden},
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Zhebin Yu
  %D 2022
  %J JAMA Netw Open.
  %R 10.1001/jamanetworkopen.2022.8109.
  %T Association of Short-term Air Pollution Exposure With SARS-CoV-2 Infection Among Young Adults in Sweden
  %U /brokenurl#10.1001/jamanetworkopen.2022.8109.
  %X Importance: Mounting ecological evidence shows an association between short-term air pollution exposure and COVID-19, yet no study has examined this association on an individual level. Objective: To estimate the association between short-term exposure to ambient air pollution and SARS-CoV-2 infection among Swedish young adults. Design, setting, and participants: This time-stratified case-crossover study linked the prospective BAMSE (Children, Allergy Milieu, Stockholm, Epidemiology [in Swedish]) birth cohort to the Swedish national infectious disease registry to identify cases with positive results for SARS-CoV-2 polymerase chain reaction (PCR) testing from May 5, 2020, to March 31, 2021. Case day was defined as the date of the PCR test, whereas the dates with the same day of the week within the same calendar month and year were selected as control days. Data analysis was conducted from September 1 to December 31, 2021. Exposures: Daily air pollutant levels (particulate matter with diameter ≤2.5 μm [PM2.5], particulate matter with diameter ≤10 μm [PM10], black carbon [BC], and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion models with high spatiotemporal resolution. Main outcomes and measures: Confirmed SARS-CoV-2 infection among participants within the BAMSE cohort. Distributed-lag models combined with conditional logistic regression models were used to estimate the association. Results: A total of 425 cases were identified, of whom 229 (53.9%) were women, and the median age was 25.6 (IQR, 24.9-26.3) years. The median exposure level for PM2.5 was 4.4 [IQR, 2.6-6.8] μg/m3 on case days; for PM10, 7.7 [IQR, 4.6-11.3] μg/m3 on case days; for BC, 0.3 [IQR, 0.2-0.5] μg/m3 on case days; and for NOx, 8.2 [5.6-14.1] μg/m3 on case days. Median exposure levels on control days were 3.8 [IQR, 2.4-5.9] μg/m3 for PM2.5, 6.6 [IQR, 4.5-10.4] μg/m3 for PM10, 0.2 [IQR, 0.2-0.4] μg/m3 for BC, and 7.7 [IQR, 5.3-12.8] μg/m3 for NOx. Each IQR increase in short-term exposure to PM2.5 on lag 2 was associated with a relative increase in positive results of SARS-CoV-2 PCR testing of 6.8% (95% CI, 2.1%-11.8%); exposure to PM10 on lag 2, 6.9% (95% CI, 2.0%-12.1%); and exposure to BC on lag 1, 5.8% (95% CI, 0.3%-11.6%). These findings were not associated with NOx, nor were they modified by sex, smoking, or having asthma, overweight, or self-reported COVID-19 respiratory symptoms. Conclusions and relevance: The findings of this case-crossover study of Swedish young adults suggest that short-term exposure to particulate matter and BC was associated with increased risk of positive PRC test results for SARS-CoV-2, supporting the broad public health benefits of reducing ambient air pollution levels.
  

• 1.

  P, B., and M, A. (2022) Severe acute hepatitis in children: investigate SARS-CoV-2 superantigens, Lancet.

  URLBibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {P, Brodin and M, Arditi},
  journal = {Lancet},
  keywords = {Severe acute hepatitis},
  title = {Severe acute hepatitis in children: investigate SARS-CoV-2 superantigens},
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A P, Brodin
  %A M, Arditi
  %D 2022
  %J Lancet
  %R https://doi.org/10.1016/ S2468-1253(22)00166-2
  %T Severe acute hepatitis in children: investigate SARS-CoV-2 superantigens
  %U https://doi.org/10.1016/ S2468-1253(22)00166-2
  

• 1.

  Brodin, P. (2022) Immune-microbe interactions early in life: A determinant of health and disease long term, Science, American Association for the Advancement of Science (AAAS) 376, 945–950.

  URLBibTeXEndNoteDOIBibSonomy

  @article{Brodin_2022,
  author = {Brodin, Petter},
  journal = {Science},
  keywords = {Immune-microbe interactions},
  month = {may},
  number = 6596,
  pages = {945--950},
  publisher = {American Association for the Advancement of Science (AAAS)},
  title = {Immune-microbe interactions early in life: A determinant of health and disease long term},
  volume = 376,
  year = 2022
  }
  

  %0 Journal Article
  %1 Brodin_2022
  %A Brodin, Petter
  %D 2022
  %I American Association for the Advancement of Science (AAAS)
  %J Science
  %N 6596
  %P 945--950
  %R 10.1126/science.abk2189
  %T Immune-microbe interactions early in life: A determinant of health and disease long term
  %U https://doi.org/10.1126%2Fscience.abk2189
  %V 376
  

• 1.

  et al., E. W. B. (2022) Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors, J Clin Immunol..

  AbstractBibTeXEndNoteDOIBibSonomy

  Purpose: The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors. Methods: Mass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans. Results: Overall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-ɣ and CXCL10 were downregulated. Conclusions: The clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.

  @article{noauthororeditor,
  abstract = {Purpose: The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors. Methods: Mass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans. Results: Overall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-ɣ and CXCL10 were downregulated. Conclusions: The clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.},
  author = {et al., Emilie W Borgström},
  journal = {J Clin Immunol.},
  keywords = {Inhibitors JAK},
  title = {Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors},
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al., Emilie W Borgström
  %D 2022
  %J J Clin Immunol.
  %R 10.1007/s10875-022-01351-0
  %T Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors
  %X Purpose: The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors. Methods: Mass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans. Results: Overall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-ɣ and CXCL10 were downregulated. Conclusions: The clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.
  

• 1.

  et al, S. D. (2022) Selective transfer of maternal antibodies in preterm and fullterm children, Sci Rep. 12, 14937.

  AbstractBibTeXEndNoteDOIBibSonomy

  Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-specific development remains unclear. To begin to define whether maternal-fetal antibody transfer profiles differ across preterm (PT) and fullterm (FT) infants, the overall quantity and functional quality of an array of 24 vaccine-, endemic pathogen-, and common antigen-specific antibodies were assessed across a cohort of 11 PT and 12 term-delivered maternal:infant pairs from birth through week 12. While total IgG levels to influenza, pneumo, measles, rubella, EBV, and RSV were higher in FT newborns, selective Fc-receptor binding antibodies was noted in PT newborns. In fact, near equivalent antibody-effector functions were observed across PT and FT infants, despite significant quantitative differences in transferred antibody levels. Moreover, temporal transfer analysis revealed the selective early transfer of FcRn, FcγR2, and FcγR3 binding antibodies, pointing to differential placental sieving mechanisms across gestation. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm.

  @article{noauthororeditor,
  abstract = {Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-specific development remains unclear. To begin to define whether maternal-fetal antibody transfer profiles differ across preterm (PT) and fullterm (FT) infants, the overall quantity and functional quality of an array of 24 vaccine-, endemic pathogen-, and common antigen-specific antibodies were assessed across a cohort of 11 PT and 12 term-delivered maternal:infant pairs from birth through week 12. While total IgG levels to influenza, pneumo, measles, rubella, EBV, and RSV were higher in FT newborns, selective Fc-receptor binding antibodies was noted in PT newborns. In fact, near equivalent antibody-effector functions were observed across PT and FT infants, despite significant quantitative differences in transferred antibody levels. Moreover, temporal transfer analysis revealed the selective early transfer of FcRn, FcγR2, and FcγR3 binding antibodies, pointing to differential placental sieving mechanisms across gestation. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm.},
  author = {et al, Sepideh Dolatshahi},
  journal = {Sci Rep.},
  keywords = {antibodies maternal},
  month = {sep},
  number = 1,
  pages = 14937,
  title = {Selective transfer of maternal antibodies in preterm and fullterm children},
  volume = 12,
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Sepideh Dolatshahi
  %D 2022
  %J Sci Rep.
  %N 1
  %P 14937
  %R 10.1038/s41598-022-18973-4
  %T Selective transfer of maternal antibodies in preterm and fullterm children
  %V 12
  %X Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-specific development remains unclear. To begin to define whether maternal-fetal antibody transfer profiles differ across preterm (PT) and fullterm (FT) infants, the overall quantity and functional quality of an array of 24 vaccine-, endemic pathogen-, and common antigen-specific antibodies were assessed across a cohort of 11 PT and 12 term-delivered maternal:infant pairs from birth through week 12. While total IgG levels to influenza, pneumo, measles, rubella, EBV, and RSV were higher in FT newborns, selective Fc-receptor binding antibodies was noted in PT newborns. In fact, near equivalent antibody-effector functions were observed across PT and FT infants, despite significant quantitative differences in transferred antibody levels. Moreover, temporal transfer analysis revealed the selective early transfer of FcRn, FcγR2, and FcγR3 binding antibodies, pointing to differential placental sieving mechanisms across gestation. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm.
  

• 1.

  et al., C. P. (2022) Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation, Cell Rep. 39, 110989.

  AbstractBibTeXEndNoteDOIBibSonomy

  The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon β (IFNβ) is a major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulating monocytes. Integrative modeling of proteomic, genetic, epigenomic, and cellular data confirms IFNβ as key for LPS-induced IL-12p70 and allowed us to compare the relative effects of each of these parameters on variable cytokine responses. Clinical relevance of our findings is supported by reduced IFNβ-IL-12p70 responses in patients hospitalized with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or chronically infected with hepatitis C (HCV). Importantly, these responses are resolved after viral clearance. Our systems immunology approach defines a better understanding of IL-12p70 and IFNβ in healthy and infected persons, providing insights into how common genetic and epigenetic variation may impact immune responses to bacterial infection.

  @article{noauthororeditor,
  abstract = {The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon β (IFNβ) is a major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulating monocytes. Integrative modeling of proteomic, genetic, epigenomic, and cellular data confirms IFNβ as key for LPS-induced IL-12p70 and allowed us to compare the relative effects of each of these parameters on variable cytokine responses. Clinical relevance of our findings is supported by reduced IFNβ-IL-12p70 responses in patients hospitalized with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or chronically infected with hepatitis C (HCV). Importantly, these responses are resolved after viral clearance. Our systems immunology approach defines a better understanding of IL-12p70 and IFNβ in healthy and infected persons, providing insights into how common genetic and epigenetic variation may impact immune responses to bacterial infection.},
  author = {et al., Celine Posseme},
  journal = {Cell Rep.},
  keywords = {TLR4 activation},
  month = {Jun 28},
  number = 13,
  pages = 110989,
  title = {Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation},
  volume = 39,
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al., Celine Posseme
  %D 2022
  %J Cell Rep.
  %N 13
  %P 110989
  %R 10.1016/j.celrep.2022.110989
  %T Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation
  %V 39
  %X The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon β (IFNβ) is a major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulating monocytes. Integrative modeling of proteomic, genetic, epigenomic, and cellular data confirms IFNβ as key for LPS-induced IL-12p70 and allowed us to compare the relative effects of each of these parameters on variable cytokine responses. Clinical relevance of our findings is supported by reduced IFNβ-IL-12p70 responses in patients hospitalized with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or chronically infected with hepatitis C (HCV). Importantly, these responses are resolved after viral clearance. Our systems immunology approach defines a better understanding of IL-12p70 and IFNβ in healthy and infected persons, providing insights into how common genetic and epigenetic variation may impact immune responses to bacterial infection.
  

• 1.

  et al., J. C. (2022) Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity, Mol Oncol ..

  AbstractBibTeXEndNoteDOIBibSonomy

  Prostate cancer is a heterogeneous disease with a need for new prognostic biomarkers. Human leukocyte antigen (HLA) genes are highly polymorphic genes central to antigen presentation to T-cells. Two alleles, HLA-A*02:01 and HLA-A*24:02, have been associated with prognosis in patients diagnosed with de novo metastatic prostate cancer. We leveraged the next-generation sequenced cohorts CPC-GENE and TCGA-PRAD to examine HLA alleles, antiviral T-cell receptors and prostate cancer disease recurrence after prostatectomy. Carrying HLA-A*02:01 (111/229; 48% of patients) was independently associated with disease recurrence in patients with low-intermediate risk prostate cancer. HLA-A*11 (carried by 42/441; 10% of patients) was independently associated with rapid disease recurrence in patients with high-risk prostate cancer. Moreover, HLA-A*02:01 carriers in which anti-cytomegalovirus T-cell receptors (CMV-TCR) were identified in tumors (13/144; 10% of all patients in the cohort) had a higher risk of disease recurrence than CMV-TCR-negative patients. These findings suggest that HLA-type and CMV immunity may be valuable biomarkers for prostate cancer progression.

  @article{noauthororeditor,
  abstract = {Prostate cancer is a heterogeneous disease with a need for new prognostic biomarkers. Human leukocyte antigen (HLA) genes are highly polymorphic genes central to antigen presentation to T-cells. Two alleles, HLA-A*02:01 and HLA-A*24:02, have been associated with prognosis in patients diagnosed with de novo metastatic prostate cancer. We leveraged the next-generation sequenced cohorts CPC-GENE and TCGA-PRAD to examine HLA alleles, antiviral T-cell receptors and prostate cancer disease recurrence after prostatectomy. Carrying HLA-A*02:01 (111/229; 48% of patients) was independently associated with disease recurrence in patients with low-intermediate risk prostate cancer. HLA-A*11 (carried by 42/441; 10% of patients) was independently associated with rapid disease recurrence in patients with high-risk prostate cancer. Moreover, HLA-A*02:01 carriers in which anti-cytomegalovirus T-cell receptors (CMV-TCR) were identified in tumors (13/144; 10% of all patients in the cohort) had a higher risk of disease recurrence than CMV-TCR-negative patients. These findings suggest that HLA-type and CMV immunity may be valuable biomarkers for prostate cancer progression.},
  author = {et al., Johanna Classon},
  journal = {Mol Oncol .},
  keywords = {Prostate cancer},
  month = {June 16},
  title = {Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity},
  year = 2022
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al., Johanna Classon
  %D 2022
  %J Mol Oncol .
  %R 10.1002/1878-0261.13273
  %T Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity
  %X Prostate cancer is a heterogeneous disease with a need for new prognostic biomarkers. Human leukocyte antigen (HLA) genes are highly polymorphic genes central to antigen presentation to T-cells. Two alleles, HLA-A*02:01 and HLA-A*24:02, have been associated with prognosis in patients diagnosed with de novo metastatic prostate cancer. We leveraged the next-generation sequenced cohorts CPC-GENE and TCGA-PRAD to examine HLA alleles, antiviral T-cell receptors and prostate cancer disease recurrence after prostatectomy. Carrying HLA-A*02:01 (111/229; 48% of patients) was independently associated with disease recurrence in patients with low-intermediate risk prostate cancer. HLA-A*11 (carried by 42/441; 10% of patients) was independently associated with rapid disease recurrence in patients with high-risk prostate cancer. Moreover, HLA-A*02:01 carriers in which anti-cytomegalovirus T-cell receptors (CMV-TCR) were identified in tumors (13/144; 10% of all patients in the cohort) had a higher risk of disease recurrence than CMV-TCR-negative patients. These findings suggest that HLA-type and CMV immunity may be valuable biomarkers for prostate cancer progression.
  

• 1.

  Zhang, Q., Matuozzo, D., Pen, J. L., Lee, D., Moens, L., Asano, T., Bohlen, J., Liu, Z., Moncada-Velez, M., Kendir-Demirkol, Y., Jing, H., Bizien, L., Marchal, A., Abolhassani, H., Delafontaine, S., Bucciol, G., Abel, L., Abolhassani, H., Aiuti, A., Akcan, O. M., Al-Muhsen, S., Al-Mulla, F., Alkan, G., Anderson, M. S., Andreakos, E., Arias, A. A., Bakkouri, J. E., Feldman, H. B., Belot, A., Biggs, C. M., Bogunovic, D., Bolze, A., Bondarenko, A., Bousfiha, A. A., Bozdemir, S. E., Brodin, P., Bryceson, Y., Bustamante, C. D., Butte, M. J., Casari, G., Christodoulou, J., Colobran, R., Condino-Neto, A., Constantinescu, S. N., Cooper, M. A., Dalgard, C. L., Desai, M., Drolet, B. A., Baghdadi, J. E., Emiroglu, M., Erdeniz, E. H., Espinosa-Padilla, S., Fellay, J., Flores, C., Franco, J. L., Froidure, A., Gregersen, P. K., Grimbacher, B., Gulhan, B., Haerynck, F., Hagin, D., Halwani, R., Hammarström, L., Heath, J. R., Henrickson, S. E., Hsieh, E. W., Husebye, E., Imai, K., Itan, Y., Jabandziev, P., Jarvis, E. D., Karamitros, T., Karbuz, A., Kisand, K., Ku, C.-L., Lau, Y.-L., Ling, Y., Lucas, C. L., Maniatis, T., Mansouri, D., Maródi, L., Metin, A., Meyts, I., Milner, J. D., Mironska, K., Mogensen, T. H., Morio, T., Ng, L. F., Notarangelo, L. D., Novelli, A., Novelli, G., OtextquotesingleFarrelly, C., Okada, S., Okamoto, K., Öz, Şadiye K. T., Ozcelik, T., Pan-Hammarström, Q., Papadaki, M., Pape, J. W., Parlakay, A. O., de Diego, R. P., Perlin, D. S., Pesole, G., Planas, A. M., Pokorna, P., Prando, C., Pujol, A., Quintana-Murci, L., Ramaswamy, S., Renia, L., Resnick, I., Rivière, J. G., Rodr’iguez-Gallego, C., Sancho-Shimizu, V., Sediva, A., Seppänen, M. R., Shahrooei, M., Shcherbina, A., Slaba, K., Slaby, O., Snow, A. L., Soler-Palac’in, P., Somer, L. D., Spaan, A. N., Tancevski, I., Tangye, S. G., Tayoun, A. A., Thanos, D., Turvey, S. E., Uddin, K. M. F., Uddin, M. J., van de Beek, D., Vermeulen, F., Vinh, D. C., von Bernuth, H., Wauters, J., Wouters, C., Yahsi, A., Yuksek, S. K., Zatz, M., Zawadzki, P., Su, H. C., Casanova, J.-L., Bayhan, G. I., Keles, S., Kiykim, A., Hancerli, S., Haerynck, F., Florkin, B., Hatipoglu, N., Ozcelik, T., Morelle, G., Zatz, M., Ng, L. F., Lye, D. C., Young, B. E., Leo, Y.-S., Dalgard, C. L., Lifton, R. P., Renia, L., Meyts, I., Jouanguy, E., Hammarström, L., Pan-Hammarström, Q., Boisson, B., Bastard, P., Su, H. C., Boisson-Dupuis, S., Abel, L., Rice, C. M., Zhang, S.-Y., Cobat, A., and Casanova, J.-L. (2022) Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia, Journal of Experimental Medicine, Rockefeller University Press 219.

  URLBibTeXEndNoteDOIBibSonomy

  @article{Zhang_2022,
  author = {Zhang, Qian and Matuozzo, Daniela and Pen, Jérémie Le and Lee, Danyel and Moens, Leen and Asano, Takaki and Bohlen, Jonathan and Liu, Zhiyong and Moncada-Velez, Marcela and Kendir-Demirkol, Yasemin and Jing, Huie and Bizien, Lucy and Marchal, Astrid and Abolhassani, Hassan and Delafontaine, Selket and Bucciol, Giorgia and Abel, Laurent and Abolhassani, Hassan and Aiuti, Alessandro and Akcan, Ozge Metin and Al-Muhsen, Saleh and Al-Mulla, Fahd and Alkan, Gulsum and Anderson, Mark S. and Andreakos, Evangelos and Arias, Andrés A. and Bakkouri, Jalila El and Feldman, Hagit Baris and Belot, Alexandre and Biggs, Catherine M. and Bogunovic, Dusan and Bolze, Alexandre and Bondarenko, Anastasiia and Bousfiha, Ahmed A. and Bozdemir, Sefika Elmas and Brodin, Petter and Bryceson, Yenan and Bustamante, Carlos D. and Butte, Manish J. and Casari, Giorgio and Christodoulou, John and Colobran, Roger and Condino-Neto, Antonio and Constantinescu, Stefan N. and Cooper, Megan A. and Dalgard, Clifton L. and Desai, Murkesh and Drolet, Beth A. and Baghdadi, Jamila El and Emiroglu, Melike and Erdeniz, Emine Hafize and Espinosa-Padilla, Sara and Fellay, Jacques and Flores, Carlos and Franco, José Luis and Froidure, Antoine and Gregersen, Peter K. and Grimbacher, Bodo and Gulhan, Belgin and Haerynck, Filomeen and Hagin, David and Halwani, Rabih and Hammarström, Lennart and Heath, James R. and Henrickson, Sarah E. and Hsieh, Elena W.Y. and Husebye, Eystein and Imai, Kohsuke and Itan, Yuval and Jabandziev, Petr and Jarvis, Erich D. and Karamitros, Timokratis and Karbuz, Adem and Kisand, Kai and Ku, Cheng-Lung and Lau, Yu-Lung and Ling, Yun and Lucas, Carrie L. and Maniatis, Tom and Mansouri, Davood and Maródi, László and Metin, Ayse and Meyts, Isabelle and Milner, Joshua D. and Mironska, Kristina and Mogensen, Trine H. and Morio, Tomohiro and Ng, Lisa F.P. and Notarangelo, Luigi D. and Novelli, Antonio and Novelli, Giuseppe and OtextquotesingleFarrelly, Cliona and Okada, Satoshi and Okamoto, Keisuke and Öz, Şadiye Kübra Tüter and Ozcelik, Tayfun and Pan-Hammarström, Qiang and Papadaki, Maria and Pape, Jean W. and Parlakay, Aslinur Ozkaya and de Diego, Rebeca Perez and Perlin, David S. and Pesole, Graziano and Planas, Anna M. and Pokorna, Petra and Prando, Carolina and Pujol, Aurora and Quintana-Murci, Lluis and Ramaswamy, Sathishkumar and Renia, Laurent and Resnick, Igor and Rivière, Jacques G. and Rodr'iguez-Gallego, Carlos and Sancho-Shimizu, Vanessa and Sediva, Anna and Seppänen, Mikko R.J. and Shahrooei, Mohammed and Shcherbina, Anna and Slaba, Katerina and Slaby, Ondrej and Snow, Andrew L. and Soler-Palac'in, Pere and Somer, Lien De and Spaan, András N. and Tancevski, Ivan and Tangye, Stuart G. and Tayoun, Ahmad Abou and Thanos, Dimitris and Turvey, Stuart E. and Uddin, K M Furkan and Uddin, Mohammed J. and van de Beek, Diederik and Vermeulen, François and Vinh, Donald C. and von Bernuth, Horst and Wauters, Joost and Wouters, Carine and Yahsi, Aysun and Yuksek, Saliha Kanik and Zatz, Mayana and Zawadzki, Pawel and Su, Helen C. and Casanova, Jean-Laurent and Bayhan, Gulsum Ical and Keles, Sevgi and Kiykim, Ayca and Hancerli, Selda and Haerynck, Filomeen and Florkin, Benoit and Hatipoglu, Nevin and Ozcelik, Tayfun and Morelle, Guillaume and Zatz, Mayana and Ng, Lisa F.P. and Lye, David Chien and Young, Barnaby Edward and Leo, Yee-Sin and Dalgard, Clifton L. and Lifton, Richard P. and Renia, Laurent and Meyts, Isabelle and Jouanguy, Emmanuelle and Hammarström, Lennart and Pan-Hammarström, Qiang and Boisson, Bertrand and Bastard, Paul and Su, Helen C. and Boisson-Dupuis, Stéphanie and Abel, Laurent and Rice, Charles M. and Zhang, Shen-Ying and Cobat, Aurélie and Casanova, Jean-Laurent},
  journal = {Journal of Experimental Medicine},
  keywords = {I errors immunity inborn of type {IFN}},
  month = {jun},
  number = 8,
  publisher = {Rockefeller University Press},
  title = {Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia},
  volume = 219,
  year = 2022
  }
  

  %0 Journal Article
  %1 Zhang_2022
  %A Zhang, Qian
  %A Matuozzo, Daniela
  %A Pen, Jérémie Le
  %A Lee, Danyel
  %A Moens, Leen
  %A Asano, Takaki
  %A Bohlen, Jonathan
  %A Liu, Zhiyong
  %A Moncada-Velez, Marcela
  %A Kendir-Demirkol, Yasemin
  %A Jing, Huie
  %A Bizien, Lucy
  %A Marchal, Astrid
  %A Abolhassani, Hassan
  %A Delafontaine, Selket
  %A Bucciol, Giorgia
  %A Abel, Laurent
  %A Abolhassani, Hassan
  %A Aiuti, Alessandro
  %A Akcan, Ozge Metin
  %A Al-Muhsen, Saleh
  %A Al-Mulla, Fahd
  %A Alkan, Gulsum
  %A Anderson, Mark S.
  %A Andreakos, Evangelos
  %A Arias, Andrés A.
  %A Bakkouri, Jalila El
  %A Feldman, Hagit Baris
  %A Belot, Alexandre
  %A Biggs, Catherine M.
  %A Bogunovic, Dusan
  %A Bolze, Alexandre
  %A Bondarenko, Anastasiia
  %A Bousfiha, Ahmed A.
  %A Bozdemir, Sefika Elmas
  %A Brodin, Petter
  %A Bryceson, Yenan
  %A Bustamante, Carlos D.
  %A Butte, Manish J.
  %A Casari, Giorgio
  %A Christodoulou, John
  %A Colobran, Roger
  %A Condino-Neto, Antonio
  %A Constantinescu, Stefan N.
  %A Cooper, Megan A.
  %A Dalgard, Clifton L.
  %A Desai, Murkesh
  %A Drolet, Beth A.
  %A Baghdadi, Jamila El
  %A Emiroglu, Melike
  %A Erdeniz, Emine Hafize
  %A Espinosa-Padilla, Sara
  %A Fellay, Jacques
  %A Flores, Carlos
  %A Franco, José Luis
  %A Froidure, Antoine
  %A Gregersen, Peter K.
  %A Grimbacher, Bodo
  %A Gulhan, Belgin
  %A Haerynck, Filomeen
  %A Hagin, David
  %A Halwani, Rabih
  %A Hammarström, Lennart
  %A Heath, James R.
  %A Henrickson, Sarah E.
  %A Hsieh, Elena W.Y.
  %A Husebye, Eystein
  %A Imai, Kohsuke
  %A Itan, Yuval
  %A Jabandziev, Petr
  %A Jarvis, Erich D.
  %A Karamitros, Timokratis
  %A Karbuz, Adem
  %A Kisand, Kai
  %A Ku, Cheng-Lung
  %A Lau, Yu-Lung
  %A Ling, Yun
  %A Lucas, Carrie L.
  %A Maniatis, Tom
  %A Mansouri, Davood
  %A Maródi, László
  %A Metin, Ayse
  %A Meyts, Isabelle
  %A Milner, Joshua D.
  %A Mironska, Kristina
  %A Mogensen, Trine H.
  %A Morio, Tomohiro
  %A Ng, Lisa F.P.
  %A Notarangelo, Luigi D.
  %A Novelli, Antonio
  %A Novelli, Giuseppe
  %A OtextquotesingleFarrelly, Cliona
  %A Okada, Satoshi
  %A Okamoto, Keisuke
  %A Öz, Şadiye Kübra Tüter
  %A Ozcelik, Tayfun
  %A Pan-Hammarström, Qiang
  %A Papadaki, Maria
  %A Pape, Jean W.
  %A Parlakay, Aslinur Ozkaya
  %A de Diego, Rebeca Perez
  %A Perlin, David S.
  %A Pesole, Graziano
  %A Planas, Anna M.
  %A Pokorna, Petra
  %A Prando, Carolina
  %A Pujol, Aurora
  %A Quintana-Murci, Lluis
  %A Ramaswamy, Sathishkumar
  %A Renia, Laurent
  %A Resnick, Igor
  %A Rivière, Jacques G.
  %A Rodr'iguez-Gallego, Carlos
  %A Sancho-Shimizu, Vanessa
  %A Sediva, Anna
  %A Seppänen, Mikko R.J.
  %A Shahrooei, Mohammed
  %A Shcherbina, Anna
  %A Slaba, Katerina
  %A Slaby, Ondrej
  %A Snow, Andrew L.
  %A Soler-Palac'in, Pere
  %A Somer, Lien De
  %A Spaan, András N.
  %A Tancevski, Ivan
  %A Tangye, Stuart G.
  %A Tayoun, Ahmad Abou
  %A Thanos, Dimitris
  %A Turvey, Stuart E.
  %A Uddin, K M Furkan
  %A Uddin, Mohammed J.
  %A van de Beek, Diederik
  %A Vermeulen, François
  %A Vinh, Donald C.
  %A von Bernuth, Horst
  %A Wauters, Joost
  %A Wouters, Carine
  %A Yahsi, Aysun
  %A Yuksek, Saliha Kanik
  %A Zatz, Mayana
  %A Zawadzki, Pawel
  %A Su, Helen C.
  %A Casanova, Jean-Laurent
  %A Bayhan, Gulsum Ical
  %A Keles, Sevgi
  %A Kiykim, Ayca
  %A Hancerli, Selda
  %A Haerynck, Filomeen
  %A Florkin, Benoit
  %A Hatipoglu, Nevin
  %A Ozcelik, Tayfun
  %A Morelle, Guillaume
  %A Zatz, Mayana
  %A Ng, Lisa F.P.
  %A Lye, David Chien
  %A Young, Barnaby Edward
  %A Leo, Yee-Sin
  %A Dalgard, Clifton L.
  %A Lifton, Richard P.
  %A Renia, Laurent
  %A Meyts, Isabelle
  %A Jouanguy, Emmanuelle
  %A Hammarström, Lennart
  %A Pan-Hammarström, Qiang
  %A Boisson, Bertrand
  %A Bastard, Paul
  %A Su, Helen C.
  %A Boisson-Dupuis, Stéphanie
  %A Abel, Laurent
  %A Rice, Charles M.
  %A Zhang, Shen-Ying
  %A Cobat, Aurélie
  %A Casanova, Jean-Laurent
  %D 2022
  %I Rockefeller University Press
  %J Journal of Experimental Medicine
  %N 8
  %R 10.1084/jem.20220131
  %T Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia
  %U https://doi.org/10.1084%2Fjem.20220131
  %V 219
  

• 1.

  Henrick, B. M., Rodriguez, L., Lakshmikanth, T., Pou, C., Henckel, E., Arzoomand, A., Olin, A., Wang, J., Mikes, J., Tan, Z., Chen, Y., Ehrlich, A. M., Bernhardsson, A. K., Mugabo, C. H., Ambrosiani, Y., Gustafsson, A., Chew, S., Brown, H. K., Prambs, J., Bohlin, K., Mitchell, R. D., Underwood, M. A., Smilowitz, J. T., German, J. B., Frese, S. A., and Brodin, P. (2021) Bifidobacteria-mediated immune system imprinting early in life, Cell, Elsevier.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that in turn benefit the host?s immune system. Such bacteria have co-evolved with humans but are now increasingly rare in modern societies. Here we show that a lack of bifidobacteria, and in particular depletion of genes required for human milk oligosaccharide (HMO) utilization from the metagenome, is associated with systemic inflammation and immune dysregulation early in life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon ? (IFN?) was induced. Fecal water from EVC001-supplemented infants contains abundant indolelactate and B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory galectin-1 in Th2 and Th17 cells during polarization, providing a functional link between beneficial microbes and immunoregulation during the first months of life.

  @article{henrickbifidobacteriamediated,
  abstract = {Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that in turn benefit the host?s immune system. Such bacteria have co-evolved with humans but are now increasingly rare in modern societies. Here we show that a lack of bifidobacteria, and in particular depletion of genes required for human milk oligosaccharide (HMO) utilization from the metagenome, is associated with systemic inflammation and immune dysregulation early in life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon ? (IFN?) was induced. Fecal water from EVC001-supplemented infants contains abundant indolelactate and B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory galectin-1 in Th2 and Th17 cells during polarization, providing a functional link between beneficial microbes and immunoregulation during the first months of life.},
  author = {Henrick, Bethany M. and Rodriguez, Lucie and Lakshmikanth, Tadepally and Pou, Christian and Henckel, Ewa and Arzoomand, Aron and Olin, Axel and Wang, Jun and Mikes, Jaromir and Tan, Ziyang and Chen, Yang and Ehrlich, Amy M. and Bernhardsson, Anna Karin and Mugabo, Constantin Habimana and Ambrosiani, Ylva and Gustafsson, Anna and Chew, Stephanie and Brown, Heather K. and Prambs, Johann and Bohlin, Kajsa and Mitchell, Ryan D. and Underwood, Mark A. and Smilowitz, Jennifer T. and German, J. Bruce and Frese, Steven A. and Brodin, Petter},
  booktitle = {Cell},
  journal = {Cell},
  keywords = {Bifidobacterium},
  publisher = {Elsevier},
  title = {Bifidobacteria-mediated immune system imprinting early in life},
  year = 2021
  }
  

  %0 Journal Article
  %1 henrickbifidobacteriamediated
  %A Henrick, Bethany M.
  %A Rodriguez, Lucie
  %A Lakshmikanth, Tadepally
  %A Pou, Christian
  %A Henckel, Ewa
  %A Arzoomand, Aron
  %A Olin, Axel
  %A Wang, Jun
  %A Mikes, Jaromir
  %A Tan, Ziyang
  %A Chen, Yang
  %A Ehrlich, Amy M.
  %A Bernhardsson, Anna Karin
  %A Mugabo, Constantin Habimana
  %A Ambrosiani, Ylva
  %A Gustafsson, Anna
  %A Chew, Stephanie
  %A Brown, Heather K.
  %A Prambs, Johann
  %A Bohlin, Kajsa
  %A Mitchell, Ryan D.
  %A Underwood, Mark A.
  %A Smilowitz, Jennifer T.
  %A German, J. Bruce
  %A Frese, Steven A.
  %A Brodin, Petter
  %B Cell
  %D 2021
  %I Elsevier
  %J Cell
  %R 10.1016/j.cell.2021.05.030
  %T Bifidobacteria-mediated immune system imprinting early in life
  %U https://doi.org/10.1016/j.cell.2021.05.030
  %X Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that in turn benefit the host?s immune system. Such bacteria have co-evolved with humans but are now increasingly rare in modern societies. Here we show that a lack of bifidobacteria, and in particular depletion of genes required for human milk oligosaccharide (HMO) utilization from the metagenome, is associated with systemic inflammation and immune dysregulation early in life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon ? (IFN?) was induced. Fecal water from EVC001-supplemented infants contains abundant indolelactate and B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory galectin-1 in Th2 and Th17 cells during polarization, providing a functional link between beneficial microbes and immunoregulation during the first months of life.
  

• 1.

  "Yan, Z., "Maecker, H. T., "Brodin, P., "Nygaard, U. C., "Lyu, S. C., "Davis, M. M., "Nadeau, K. C., and "Andorf, S. (2021) Aging and CMV discordance are associated with increased immune diversity between monozygotic twins, Immun Ageing. 18, 1–12.

  AbstractBibTeXEndNoteDOIBibSonomy

  Background: Broadly, much of variance in immune system phenotype has been linked to the influence of non-heritable factors rather than genetics. In particular, two non-heritable factors: aging and human cytolomegavirus (CMV) infection, have been known to account for significant inter-individual immune variance. However, many specific relationships between them and immune composition remain unclear, especially between individuals over narrower age ranges. Further exploration of these relationships may be useful for informing personalized intervention development. Results: To address this need, we evaluated 41 different cell type frequencies by mass cytometry and identified their relationships with aging and CMV seropositivity. Analyses were done using 60 healthy individuals, including 23 monozygotic twin pairs, categorized into young (12-31 years) and middle-aged (42-59 years). Aging and CMV discordance were associated with increased immune diversity between monozygotic twins overall, and particularly strongly in various T cell populations. Notably, we identified 17 and 11 cell subset frequencies as relatively influenced and uninfluenced by non-heritable factors, respectively, with results that largely matched those from studies on older-aged cohorts. Next, CD4+ T cell frequency was shown to diverge with age in twins, but with lower slope than in demographically similar non-twins, suggesting that much inter-individual variance in this cell type can be attributed to interactions between genetic and environmental factors. Several cell frequencies previously associated with memory inflation, such as CD27- CD8+ T cells and CD161+ CD4+ T cells, were positively correlated with CMV seropositivity, supporting findings that CMV infection may incur rapid aging of the immune system. Conclusions: Our study confirms previous findings that aging, even within a relatively small age range and by mid-adulthood, and CMV seropositivity, both contribute significantly to inter-individual immune diversity. Notably, we identify several key immune cell subsets that vary considerably with aging, as well as others associated with memory inflation which correlate with CMV seropositivity.

  @article{2021aging,
  abstract = {Background: Broadly, much of variance in immune system phenotype has been linked to the influence of non-heritable factors rather than genetics. In particular, two non-heritable factors: aging and human cytolomegavirus (CMV) infection, have been known to account for significant inter-individual immune variance. However, many specific relationships between them and immune composition remain unclear, especially between individuals over narrower age ranges. Further exploration of these relationships may be useful for informing personalized intervention development. Results: To address this need, we evaluated 41 different cell type frequencies by mass cytometry and identified their relationships with aging and CMV seropositivity. Analyses were done using 60 healthy individuals, including 23 monozygotic twin pairs, categorized into young (12-31 years) and middle-aged (42-59 years). Aging and CMV discordance were associated with increased immune diversity between monozygotic twins overall, and particularly strongly in various T cell populations. Notably, we identified 17 and 11 cell subset frequencies as relatively influenced and uninfluenced by non-heritable factors, respectively, with results that largely matched those from studies on older-aged cohorts. Next, CD4+ T cell frequency was shown to diverge with age in twins, but with lower slope than in demographically similar non-twins, suggesting that much inter-individual variance in this cell type can be attributed to interactions between genetic and environmental factors. Several cell frequencies previously associated with memory inflation, such as CD27- CD8+ T cells and CD161+ CD4+ T cells, were positively correlated with CMV seropositivity, supporting findings that CMV infection may incur rapid aging of the immune system. Conclusions: Our study confirms previous findings that aging, even within a relatively small age range and by mid-adulthood, and CMV seropositivity, both contribute significantly to inter-individual immune diversity. Notably, we identify several key immune cell subsets that vary considerably with aging, as well as others associated with memory inflation which correlate with CMV seropositivity.},
  author = {"Yan, Zheng" and "Maecker, Holden T" and "Brodin, Petter" and "Nygaard, Unni C" and "Lyu, Shu Chen" and "Davis, Mark M" and "Nadeau, Kari C" and "Andorf, Sandra"},
  journal = {Immun Ageing.},
  keywords = {CMV},
  month = {jan},
  number = 5,
  pages = {1-12},
  title = {Aging and CMV discordance are associated with increased immune diversity between monozygotic twins},
  volume = 18,
  year = 2021
  }
  

  %0 Journal Article
  %1 2021aging
  %A "Yan, Zheng"
  %A "Maecker, Holden T"
  %A "Brodin, Petter"
  %A "Nygaard, Unni C"
  %A "Lyu, Shu Chen"
  %A "Davis, Mark M"
  %A "Nadeau, Kari C"
  %A "Andorf, Sandra"
  %D 2021
  %J Immun Ageing.
  %N 5
  %P 1-12
  %R doi: 10.1186/s12979-021-00216-1
  %T Aging and CMV discordance are associated with increased immune diversity between monozygotic twins
  %V 18
  %X Background: Broadly, much of variance in immune system phenotype has been linked to the influence of non-heritable factors rather than genetics. In particular, two non-heritable factors: aging and human cytolomegavirus (CMV) infection, have been known to account for significant inter-individual immune variance. However, many specific relationships between them and immune composition remain unclear, especially between individuals over narrower age ranges. Further exploration of these relationships may be useful for informing personalized intervention development. Results: To address this need, we evaluated 41 different cell type frequencies by mass cytometry and identified their relationships with aging and CMV seropositivity. Analyses were done using 60 healthy individuals, including 23 monozygotic twin pairs, categorized into young (12-31 years) and middle-aged (42-59 years). Aging and CMV discordance were associated with increased immune diversity between monozygotic twins overall, and particularly strongly in various T cell populations. Notably, we identified 17 and 11 cell subset frequencies as relatively influenced and uninfluenced by non-heritable factors, respectively, with results that largely matched those from studies on older-aged cohorts. Next, CD4+ T cell frequency was shown to diverge with age in twins, but with lower slope than in demographically similar non-twins, suggesting that much inter-individual variance in this cell type can be attributed to interactions between genetic and environmental factors. Several cell frequencies previously associated with memory inflation, such as CD27- CD8+ T cells and CD161+ CD4+ T cells, were positively correlated with CMV seropositivity, supporting findings that CMV infection may incur rapid aging of the immune system. Conclusions: Our study confirms previous findings that aging, even within a relatively small age range and by mid-adulthood, and CMV seropositivity, both contribute significantly to inter-individual immune diversity. Notably, we identify several key immune cell subsets that vary considerably with aging, as well as others associated with memory inflation which correlate with CMV seropositivity.
  

• 1.

  Just, D., Rasmusson, A. J., Nilsson, P., Noreland, M., Malmström, E., Brodin, P., Maanberg, A., and Cunningham, J. L. (2021) Autoantibodies against the C-terminus of Lipopolysaccharide binding protein are elevated in young adults with psychiatric disease, Psychoneuroendocrinology, Elsevier BV 126, 105162.

  URLBibTeXEndNoteDOIBibSonomy

  @article{Just_2021,
  author = {Just, David and Rasmusson, Annica J. and Nilsson, Peter and Noreland, Maria and Malmström, Emma and Brodin, Petter and Maanberg, Anna and Cunningham, Janet L.},
  journal = {Psychoneuroendocrinology},
  keywords = {autoantibodies},
  month = {apr},
  pages = 105162,
  publisher = {Elsevier BV},
  title = {Autoantibodies against the C-terminus of Lipopolysaccharide binding protein are elevated in young adults with psychiatric disease},
  volume = 126,
  year = 2021
  }
  

  %0 Journal Article
  %1 Just_2021
  %A Just, David
  %A Rasmusson, Annica J.
  %A Nilsson, Peter
  %A Noreland, Maria
  %A Malmström, Emma
  %A Brodin, Petter
  %A Maanberg, Anna
  %A Cunningham, Janet L.
  %D 2021
  %I Elsevier BV
  %J Psychoneuroendocrinology
  %P 105162
  %R 10.1016/j.psyneuen.2021.105162
  %T Autoantibodies against the C-terminus of Lipopolysaccharide binding protein are elevated in young adults with psychiatric disease
  %U https://doi.org/10.1016%2Fj.psyneuen.2021.105162
  %V 126
  

• 1.

  Cotugno, N., Ruggiero, A., Bonfante, F., Petrara, M. R., Zicari, S., Pascucci, G. R., Zangari, P., De Ioris, M. A., Santilli, V., Manno, E., Amodio, D., Bortolami, A., Pagliari, M., Concato, C., Linardos, G., Campana, A., Donà, D., Giaquinto, C., Bernardi, S., Romani, L., Pansa, P., Chiurchiú, S., Finocchi, A., Cancrini, C., Lancella, L., Cursi, L., De Luca, M., Cutrera, R., Sessa, L., Morrocchi, E., Medri, C., Putignani, L., Calò Carducci, F., D’Argenio, P., Ciofi degli Atti, M., D’Amore, C., Piccioni, L., Di Giuseppe, M., Jenkner, A., Giancotta, C., Krzysztofiak, A., Brodin, P., Rossi, P., De Rossi, A., and Palma, P. (2021) Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies, Cell Reports, Elsevier 34.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.

  @article{cotugno2021virological,
  abstract = {As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.},
  author = {Cotugno, Nicola and Ruggiero, Alessandra and Bonfante, Francesco and Petrara, Maria Raffaella and Zicari, Sonia and Pascucci, Giuseppe Rubens and Zangari, Paola and De Ioris, Maria Antonietta and Santilli, Veronica and Manno, E.C and Amodio, Donato and Bortolami, Alessio and Pagliari, Matteo and Concato, Carlo and Linardos, Giulia and Campana, Andrea and Donà, Daniele and Giaquinto, Carlo and Bernardi, Stefania and Romani, Lorenza and Pansa, Paola and Chiurchiú, Sara and Finocchi, Andrea and Cancrini, Caterina and Lancella, Laura and Cursi, Laura and De Luca, Maia and Cutrera, Renato and Sessa, Libera and Morrocchi, Elena and Medri, Chiara and Putignani, Lorenza and Calò Carducci, F.I and D’Argenio, Patrizia and Ciofi degli Atti, Marta and D’Amore, Carmen and Piccioni, Livia and Di Giuseppe, Martina and Jenkner, Alessandro and Giancotta, Carmela and Krzysztofiak, Andrzej and Brodin, Petter and Rossi, Paolo and De Rossi, Anita and Palma, Paolo},
  booktitle = {Cell Reports},
  journal = {Cell Reports},
  keywords = {SARS-Cov-2},
  month = {mar},
  number = 11,
  publisher = {Elsevier},
  title = {Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies},
  volume = 34,
  year = 2021
  }
  

  %0 Journal Article
  %1 cotugno2021virological
  %A Cotugno, Nicola
  %A Ruggiero, Alessandra
  %A Bonfante, Francesco
  %A Petrara, Maria Raffaella
  %A Zicari, Sonia
  %A Pascucci, Giuseppe Rubens
  %A Zangari, Paola
  %A De Ioris, Maria Antonietta
  %A Santilli, Veronica
  %A Manno, E.C
  %A Amodio, Donato
  %A Bortolami, Alessio
  %A Pagliari, Matteo
  %A Concato, Carlo
  %A Linardos, Giulia
  %A Campana, Andrea
  %A Donà, Daniele
  %A Giaquinto, Carlo
  %A Bernardi, Stefania
  %A Romani, Lorenza
  %A Pansa, Paola
  %A Chiurchiú, Sara
  %A Finocchi, Andrea
  %A Cancrini, Caterina
  %A Lancella, Laura
  %A Cursi, Laura
  %A De Luca, Maia
  %A Cutrera, Renato
  %A Sessa, Libera
  %A Morrocchi, Elena
  %A Medri, Chiara
  %A Putignani, Lorenza
  %A Calò Carducci, F.I
  %A D’Argenio, Patrizia
  %A Ciofi degli Atti, Marta
  %A D’Amore, Carmen
  %A Piccioni, Livia
  %A Di Giuseppe, Martina
  %A Jenkner, Alessandro
  %A Giancotta, Carmela
  %A Krzysztofiak, Andrzej
  %A Brodin, Petter
  %A Rossi, Paolo
  %A De Rossi, Anita
  %A Palma, Paolo
  %B Cell Reports
  %D 2021
  %I Elsevier
  %J Cell Reports
  %N 11
  %R 10.1016/j.celrep.2021.108852
  %T Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies
  %U https://doi.org/10.1016/j.celrep.2021.108852
  %V 34
  %X As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.
  

• 1.

  Lemarquis, A., Campbell, T., Aranda-Guillén, M., Hennings, V., Brodin, P., Kämpe, O., Blennow, K., Zetterberg, H., Wennerås, C., Eriksson, K., Landegren, N., Bryceson, Y., Berg, S., and Ekwall, O. (2021) Severe COVID-19 in an APS1 patient with interferon autoantibodies treated with plasmapheresis, Journal of Allergy and Clinical Immunology, Elsevier.

  URLBibTeXEndNoteDOIBibSonomy

  @article{lemarquissevere,
  author = {Lemarquis, Andri and Campbell, Tessa and Aranda-Guillén, Maribel and Hennings, Viktoria and Brodin, Petter and Kämpe, Olle and Blennow, Kaj and Zetterberg, Henrik and Wennerås, Christine and Eriksson, Kristina and Landegren, Nils and Bryceson, Yenan and Berg, Stefan and Ekwall, Olov},
  journal = {Journal of Allergy and Clinical Immunology},
  keywords = {IFN aAbs},
  publisher = {Elsevier},
  title = {Severe COVID-19 in an APS1 patient with interferon autoantibodies treated with plasmapheresis},
  type = {Article},
  year = 2021
  }
  

  %0 Journal Article
  %1 lemarquissevere
  %A Lemarquis, Andri
  %A Campbell, Tessa
  %A Aranda-Guillén, Maribel
  %A Hennings, Viktoria
  %A Brodin, Petter
  %A Kämpe, Olle
  %A Blennow, Kaj
  %A Zetterberg, Henrik
  %A Wennerås, Christine
  %A Eriksson, Kristina
  %A Landegren, Nils
  %A Bryceson, Yenan
  %A Berg, Stefan
  %A Ekwall, Olov
  %D 2021
  %I Elsevier
  %J Journal of Allergy and Clinical Immunology
  %R 10.1016/j.jaci.2021.03.034
  %T Severe COVID-19 in an APS1 patient with interferon autoantibodies treated with plasmapheresis
  %U https://www.jacionline.org/article/S0091-6749(21)00556-X/fulltext
  

• 1.

  Peng, K. et al. (2021) Diversity in immunogenomics: the value and the challeng, Nature Methods 18, 588–591.

  URLBibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Peng, Kerui et al},
  journal = {Nature Methods},
  keywords = {Immunogenomics},
  month = {June},
  number = 6,
  pages = {588-591},
  title = {Diversity in immunogenomics: the value and the challeng},
  volume = 18,
  year = 2021
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Peng, Kerui et al
  %D 2021
  %J Nature Methods
  %N 6
  %P 588-591
  %R 10.1038/s41592-021-01169-5.
  %T Diversity in immunogenomics: the value and the challeng
  %U /brokenurl#10.1038/s41592-021-01169-5.
  %V 18
  

• 1.

  Sancho-Shimizu, V. et al. (2021) SARS-CoV-2-related MIS-C: A key to the viral and genetic causes of Kawasaki disease?, J Exp Med 218, e20210446.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.

  @article{noauthororeditor,
  abstract = {Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.},
  author = {Sancho-Shimizu, Vanessa et al},
  journal = {J Exp Med},
  keywords = {MIS-C SARS-Cov-2},
  month = {June},
  number = 6,
  pages = {e20210446},
  title = {SARS-CoV-2-related MIS-C: A key to the viral and genetic causes of Kawasaki disease?},
  volume = 218,
  year = 2021
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Sancho-Shimizu, Vanessa et al
  %D 2021
  %J J Exp Med
  %N 6
  %P e20210446
  %R 10.1084/jem.20210446
  %T SARS-CoV-2-related MIS-C: A key to the viral and genetic causes of Kawasaki disease?
  %U /brokenurl#10.1084/jem.20210446
  %V 218
  %X Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.
  

• 1.

  Brodin, P. (2021) Viktigt att uppmärksamma MIS-A inom vuxensjukvården, Lakartidningen 118.

  BibTeXEndNoteBibSonomy

  @article{noauthororeditor,
  author = {Brodin, Petter},
  journal = {Lakartidningen},
  keywords = {MIS-A},
  month = {may},
  number = 21136,
  title = {Viktigt att uppmärksamma MIS-A inom vuxensjukvården},
  volume = 118,
  year = 2021
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Brodin, Petter
  %D 2021
  %J Lakartidningen
  %N 21136
  %T Viktigt att uppmärksamma MIS-A inom vuxensjukvården
  %V 118
  

• 1.

  Brodin, P. (2021) Immune determinants of COVID-19 disease presentation and severity, Nature Medicine 27, 28–33.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in the majority of previously healthy individuals, but can cause life-threatening disease or persistent debilitating symptoms in some cases. The most important determinant of disease severity is age, with individuals over 65 years having the greatest risk of requiring intensive care, and men are more susceptible than women. In contrast to other respiratory viral infections, young children seem to be less severely affected. It is now clear that mild to severe acute infection is not the only outcome of COVID-19, and long-lasting symptoms are also possible. In contrast to severe acute COVID-19, such ‘long COVID’ is seemingly more likely in women than in men. Also, postinfectious hyperinflammatory disease has been described as an additional outcome after SARS-CoV-2 infection. Here I discuss our current understanding of the immunological determinants of COVID-19 disease presentation and severity and relate this to known immune-system differences between young and old people and between men and women, and other factors associated with different disease presentations and severity.

  @article{brodin2021immune,
  abstract = {COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in the majority of previously healthy individuals, but can cause life-threatening disease or persistent debilitating symptoms in some cases. The most important determinant of disease severity is age, with individuals over 65 years having the greatest risk of requiring intensive care, and men are more susceptible than women. In contrast to other respiratory viral infections, young children seem to be less severely affected. It is now clear that mild to severe acute infection is not the only outcome of COVID-19, and long-lasting symptoms are also possible. In contrast to severe acute COVID-19, such ‘long COVID’ is seemingly more likely in women than in men. Also, postinfectious hyperinflammatory disease has been described as an additional outcome after SARS-CoV-2 infection. Here I discuss our current understanding of the immunological determinants of COVID-19 disease presentation and severity and relate this to known immune-system differences between young and old people and between men and women, and other factors associated with different disease presentations and severity.},
  author = {Brodin, Petter},
  journal = {Nature Medicine},
  keywords = {covid-19},
  number = 1,
  pages = {28--33},
  title = {Immune determinants of COVID-19 disease presentation and severity},
  volume = 27,
  year = 2021
  }
  

  %0 Journal Article
  %1 brodin2021immune
  %A Brodin, Petter
  %D 2021
  %J Nature Medicine
  %N 1
  %P 28--33
  %R 10.1038/s41591-020-01202-8
  %T Immune determinants of COVID-19 disease presentation and severity
  %U https://doi.org/10.1038/s41591-020-01202-8
  %V 27
  %X COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in the majority of previously healthy individuals, but can cause life-threatening disease or persistent debilitating symptoms in some cases. The most important determinant of disease severity is age, with individuals over 65 years having the greatest risk of requiring intensive care, and men are more susceptible than women. In contrast to other respiratory viral infections, young children seem to be less severely affected. It is now clear that mild to severe acute infection is not the only outcome of COVID-19, and long-lasting symptoms are also possible. In contrast to severe acute COVID-19, such ‘long COVID’ is seemingly more likely in women than in men. Also, postinfectious hyperinflammatory disease has been described as an additional outcome after SARS-CoV-2 infection. Here I discuss our current understanding of the immunological determinants of COVID-19 disease presentation and severity and relate this to known immune-system differences between young and old people and between men and women, and other factors associated with different disease presentations and severity.
  

• 1.

  Maio, M. et al. (2021) A vision of immuno-oncology: the Siena think tank of the Italian network for tumor biotherapy (NIBIT) foundation, J Exp Clin Cancer Res . 40, 1–12.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Background: The yearly Think Tank Meeting of the Italian Network for Tumor Biotherapy (NIBIT) Foundation, brings together in Siena, Tuscany (Italy), experts in immuno-oncology to review the learnings from current immunotherapy treatments, and to propose new pre-clinical and clinical investigations in selected research areas. MAIN: While immunotherapies in non-small cell lung cancer and melanoma led to practice changing therapies, the same therapies had only modest benefit for patients with other malignancies, such as mesothelioma and glioblastoma. One way to improve on current immunotherapies is to alter the sequence of each combination agent. Matching the immunotherapy to the host's immune response may thus improve the activity of the current treatments. A second approach is to combine current immunotherapies with novel agents targeting complementary mechanisms. Identifying the appropriate novel agents may require different approaches than the traditional laboratory-based discovery work. For example, artificial intelligence-based research may help focusing the search for innovative and most promising combination partners. Conclusion: Novel immunotherapies are needed in cancer patients with resistance to or relapse after current immunotherapeutic drugs. Such new treatments may include targeted agents or monoclonal antibodies to overcome the immune-suppressive tumor microenvironment. The mode of combining the novel treatments, including vaccines, needs to be matched to the patient's immune status for achieving the maximum benefit. In this scenario, specific attention should be also paid nowadays to the immune intersection between COVID-19 and cancer.

  @article{noauthororeditor,
  abstract = {Background: The yearly Think Tank Meeting of the Italian Network for Tumor Biotherapy (NIBIT) Foundation, brings together in Siena, Tuscany (Italy), experts in immuno-oncology to review the learnings from current immunotherapy treatments, and to propose new pre-clinical and clinical investigations in selected research areas. MAIN: While immunotherapies in non-small cell lung cancer and melanoma led to practice changing therapies, the same therapies had only modest benefit for patients with other malignancies, such as mesothelioma and glioblastoma. One way to improve on current immunotherapies is to alter the sequence of each combination agent. Matching the immunotherapy to the host's immune response may thus improve the activity of the current treatments. A second approach is to combine current immunotherapies with novel agents targeting complementary mechanisms. Identifying the appropriate novel agents may require different approaches than the traditional laboratory-based discovery work. For example, artificial intelligence-based research may help focusing the search for innovative and most promising combination partners. Conclusion: Novel immunotherapies are needed in cancer patients with resistance to or relapse after current immunotherapeutic drugs. Such new treatments may include targeted agents or monoclonal antibodies to overcome the immune-suppressive tumor microenvironment. The mode of combining the novel treatments, including vaccines, needs to be matched to the patient's immune status for achieving the maximum benefit. In this scenario, specific attention should be also paid nowadays to the immune intersection between COVID-19 and cancer.},
  author = {Maio, M et al.},
  journal = {J Exp Clin Cancer Res .},
  keywords = {Immuno Oncology},
  month = {July},
  number = 1,
  pages = {1-12},
  title = {A vision of immuno-oncology: the Siena think tank of the Italian network for tumor biotherapy (NIBIT) foundation},
  volume = 40,
  year = 2021
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Maio, M et al.
  %D 2021
  %J J Exp Clin Cancer Res .
  %N 1
  %P 1-12
  %R https://doi.org/10.1186/s13046-021-02023-4
  %T A vision of immuno-oncology: the Siena think tank of the Italian network for tumor biotherapy (NIBIT) foundation
  %U https://doi.org/10.1186/s13046-021-02023-4
  %V 40
  %X Background: The yearly Think Tank Meeting of the Italian Network for Tumor Biotherapy (NIBIT) Foundation, brings together in Siena, Tuscany (Italy), experts in immuno-oncology to review the learnings from current immunotherapy treatments, and to propose new pre-clinical and clinical investigations in selected research areas. MAIN: While immunotherapies in non-small cell lung cancer and melanoma led to practice changing therapies, the same therapies had only modest benefit for patients with other malignancies, such as mesothelioma and glioblastoma. One way to improve on current immunotherapies is to alter the sequence of each combination agent. Matching the immunotherapy to the host's immune response may thus improve the activity of the current treatments. A second approach is to combine current immunotherapies with novel agents targeting complementary mechanisms. Identifying the appropriate novel agents may require different approaches than the traditional laboratory-based discovery work. For example, artificial intelligence-based research may help focusing the search for innovative and most promising combination partners. Conclusion: Novel immunotherapies are needed in cancer patients with resistance to or relapse after current immunotherapeutic drugs. Such new treatments may include targeted agents or monoclonal antibodies to overcome the immune-suppressive tumor microenvironment. The mode of combining the novel treatments, including vaccines, needs to be matched to the patient's immune status for achieving the maximum benefit. In this scenario, specific attention should be also paid nowadays to the immune intersection between COVID-19 and cancer.
  

• 1.

  Silva, C. S., Sundling, C., Folkesson, E., Fröberg, G., Nobrega, C., Canto-Gomes, J., Chambers, B. J., Lakshmikanth, T., Brodin, P., Bruchfeld, J., Nigou, J., Correia-Neves, M., and Källenius, G. (2021) High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids, Frontiers in Immunology, Frontiers.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Upon infection with Mycobacterium tuberculosis (Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+ leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and PPD. At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both proinflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.

  @article{silva2021dimensional,
  abstract = {Upon infection with Mycobacterium tuberculosis (Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+ leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and PPD. At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both proinflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.},
  author = {Silva, Carolina S. and Sundling, Christopher and Folkesson, Elin and Fröberg, Gabrielle and Nobrega, Claudia and Canto-Gomes, João and Chambers, Benedict J. and Lakshmikanth, Tadepally and Brodin, Petter and Bruchfeld, Judith and Nigou, Jérôme and Correia-Neves, Margarida and Källenius, Gunilla},
  journal = {Frontiers in Immunology},
  keywords = {TB},
  publisher = {Frontiers},
  title = {High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids},
  type = {article},
  year = 2021
  }
  

  %0 Journal Article
  %1 silva2021dimensional
  %A Silva, Carolina S.
  %A Sundling, Christopher
  %A Folkesson, Elin
  %A Fröberg, Gabrielle
  %A Nobrega, Claudia
  %A Canto-Gomes, João
  %A Chambers, Benedict J.
  %A Lakshmikanth, Tadepally
  %A Brodin, Petter
  %A Bruchfeld, Judith
  %A Nigou, Jérôme
  %A Correia-Neves, Margarida
  %A Källenius, Gunilla
  %D 2021
  %I Frontiers
  %J Frontiers in Immunology
  %R 10.3389/fimmu.2021.727300
  %T High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
  %U https://www.frontiersin.org/articles/10.3389/fimmu.2021.727300/full
  %X Upon infection with Mycobacterium tuberculosis (Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+ leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and PPD. At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both proinflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.
  

• 1.

  Björkander, S., Du, L., Zuo, F., Ekström, S., Wang, Y., Wan, H., Sherina, N., Schoutens, L., Andréll, J., Andersson, N., Georgelis, A., Bergström, A., Marcotte, H., Kull, I., Hammarström, L., Melén, E., Pan-Hammarström, Q., Almqvist, C., Ballardini, N., Brodin, P., Castel, A., Hallberg, J., Jansson, C., Kere, M., Lauber, A., Lövquist, A., Mjösberg, J., Mogensen, I., Palmberg, L., Pershagen, G., Roxhed, N., and Schwenk, J. (2021) SARS-CoV-2–specific B- and T-cell immunity in a population-based study of young Swedish adults, Journal of Allergy and Clinical Immunology, Elsevier.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Background

  Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear.

  Objective

  We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults.

  Methods

  We invited participants from the Swedish BAMSE (Barn [Children], Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 follow-up. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain–specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2–specific memory B- and T-cell responses were detected for a subpopulation (n = 108) by ELISpot and FluoroSpot.

  Results

  A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARS-CoV-2 specific B- and T-cell responses, respectively. B- and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects.

  Conclusions

  Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued.

  @article{bjorkandersarscov2specific,
  abstract = {

  Background

  Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear.

  Objective

  We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults.

  Methods

  We invited participants from the Swedish BAMSE (Barn [Children], Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 follow-up. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain–specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2–specific memory B- and T-cell responses were detected for a subpopulation (n = 108) by ELISpot and FluoroSpot.

  Results

  A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARS-CoV-2 specific B- and T-cell responses, respectively. B- and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects.

  Conclusions

  Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued.

  },
  author = {Björkander, Sophia and Du, Likun and Zuo, Fanglei and Ekström, Sandra and Wang, Yating and Wan, Hui and Sherina, Natalia and Schoutens, Lisanne and Andréll, Juni and Andersson, Niklas and Georgelis, Antonios and Bergström, Anna and Marcotte, Harold and Kull, Inger and Hammarström, Lennart and Melén, Erik and Pan-Hammarström, Qiang and Almqvist, Catarina and Ballardini, Natalia and Brodin, Petter and Castel, Anna and Hallberg, Jenny and Jansson, Christer and Kere, Maura and Lauber, André and Lövquist, Alexandra and Mjösberg, Jenny and Mogensen, Ida and Palmberg, Lena and Pershagen, Göran and Roxhed, Niclas and Schwenk, Jochen},
  journal = {Journal of Allergy and Clinical Immunology},
  keywords = {SARS-Cov-2},
  publisher = {Elsevier},
  title = {SARS-CoV-2–specific B- and T-cell immunity in a population-based study of young Swedish adults},
  type = {Article},
  year = 2021
  }
  

  %0 Journal Article
  %1 bjorkandersarscov2specific
  %A Björkander, Sophia
  %A Du, Likun
  %A Zuo, Fanglei
  %A Ekström, Sandra
  %A Wang, Yating
  %A Wan, Hui
  %A Sherina, Natalia
  %A Schoutens, Lisanne
  %A Andréll, Juni
  %A Andersson, Niklas
  %A Georgelis, Antonios
  %A Bergström, Anna
  %A Marcotte, Harold
  %A Kull, Inger
  %A Hammarström, Lennart
  %A Melén, Erik
  %A Pan-Hammarström, Qiang
  %A Almqvist, Catarina
  %A Ballardini, Natalia
  %A Brodin, Petter
  %A Castel, Anna
  %A Hallberg, Jenny
  %A Jansson, Christer
  %A Kere, Maura
  %A Lauber, André
  %A Lövquist, Alexandra
  %A Mjösberg, Jenny
  %A Mogensen, Ida
  %A Palmberg, Lena
  %A Pershagen, Göran
  %A Roxhed, Niclas
  %A Schwenk, Jochen
  %D 2021
  %I Elsevier
  %J Journal of Allergy and Clinical Immunology
  %R 10.1016/j.jaci.2021.10.014
  %T SARS-CoV-2–specific B- and T-cell immunity in a population-based study of young Swedish adults
  %U https://www.jacionline.org/article/S0091-6749(21)01626-2/fulltext
  %X

  Background

  Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear.

  Objective

  We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults.

  Methods

  We invited participants from the Swedish BAMSE (Barn [Children], Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 follow-up. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain–specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2–specific memory B- and T-cell responses were detected for a subpopulation (n = 108) by ELISpot and FluoroSpot.

  Results

  A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARS-CoV-2 specific B- and T-cell responses, respectively. B- and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects.

  Conclusions

  Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued.

  
  

• 1.

  et al., K. R. (2021) Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms, Acta Paediatrica.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {et al., Kahn R},
  journal = {Acta Paediatrica},
  keywords = {Covid-19 MIS-C},
  title = {Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms},
  year = 2021
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al., Kahn R
  %D 2021
  %J Acta Paediatrica
  %R https://doi.org/10.1111/apa.16191
  %T Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms
  

• 1.

  et al, A. T. (2021) X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19, Sci Immunol.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {et al, Asano T},
  journal = {Sci Immunol},
  keywords = {Covid-19},
  title = {X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19},
  year = 2021
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Asano T
  %D 2021
  %J Sci Immunol
  %R doi: 10.1126/sciimmunol.abl4348.
  %T X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19
  

• 1.

  Andreakos, E. et al. (2021) A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection., Nat Immunol.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.

  @article{noauthororeditor,
  abstract = {SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.},
  author = {Andreakos, E et al.},
  journal = {Nat Immunol},
  keywords = {SARS-Cov-2},
  title = {A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection.},
  year = 2021
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Andreakos, E et al.
  %D 2021
  %J Nat Immunol
  %R https://doi.org/10.1038/s41590-021-01030-z
  %T A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection.
  %U https://doi.org/10.1038/s41590-021-01030-z
  %X SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.
  

• 1.

  Bastard, et al. (2021) Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths, Science Immunology 6.

  AbstractBibTeXEndNoteDOIBibSonomy

  Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.

  @article{noauthororeditor,
  abstract = {Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.},
  author = {Bastard, et al},
  journal = {Science Immunology},
  keywords = {Autoantibodies},
  month = {August},
  number = 62,
  title = {Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths},
  volume = 6,
  year = 2021
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Bastard, et al
  %D 2021
  %J Science Immunology
  %N 62
  %R 10.1126/sciimmunol.abl4340
  %T Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
  %V 6
  %X Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.
  

• 1.

  McArdle, et al. (2021) Treatment of Multisystem Inflammatory Syndrome in Children, N Engl J Med. 385, 11–22.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  BACKGROUND Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union’s Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370. opens in new tab.)

  @article{noauthororeditor,
  abstract = {BACKGROUND Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union’s Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370. opens in new tab.)},
  author = {McArdle, et al},
  journal = {N Engl J Med.},
  keywords = {MIS-C},
  month = {July},
  number = 1,
  pages = {11-22},
  title = {Treatment of Multisystem Inflammatory Syndrome in Children},
  volume = 385,
  year = 2021
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A McArdle, et al
  %D 2021
  %J N Engl J Med.
  %N 1
  %P 11-22
  %R 10.1056/NEJMoa2102968
  %T Treatment of Multisystem Inflammatory Syndrome in Children
  %U https://www.nejm.org/doi/10.1056/NEJMoa2102968?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
  %V 385
  %X BACKGROUND Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union’s Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370. opens in new tab.)
  

• 1.

  et al, A. (2021) From Your Nose to Your Toes: A Review of Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic‒Associated Pernio, Journal of Investigative Dermatology.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Despite thousands of reported patients with pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative linkage to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pernio in uninfected children is associated with monogenic disorders of excessive IFN-1 immunity, whereas severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover, SARS-CoV-2 spike protein and robust IFN-1 response are seen in the skin of patients with pandemicassociated pernio, suggesting an excessive innate immune skin response to SARS-CoV-2. Understanding the pathophysiology of this phenomenon may elucidate the host mechanisms that drive a resilient immune response to SARS-CoV-2 and could produce relevant therapeutic targets.

  @article{noauthororeditor,
  abstract = {Despite thousands of reported patients with pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative linkage to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pernio in uninfected children is associated with monogenic disorders of excessive IFN-1 immunity, whereas severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover, SARS-CoV-2 spike protein and robust IFN-1 response are seen in the skin of patients with pandemicassociated pernio, suggesting an excessive innate immune skin response to SARS-CoV-2. Understanding the pathophysiology of this phenomenon may elucidate the host mechanisms that drive a resilient immune response to SARS-CoV-2 and could produce relevant therapeutic targets.},
  author = {et al, Arkin},
  journal = {Journal of Investigative Dermatology},
  keywords = {Covid-19},
  title = {From Your Nose to Your Toes: A Review of Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic‒Associated Pernio},
  year = 2021
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A et al, Arkin
  %D 2021
  %J Journal of Investigative Dermatology
  %R 10.1016/j.jid.2021.05.024
  %T From Your Nose to Your Toes: A Review of Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic‒Associated Pernio
  %U /brokenurl#10.1016/j.jid.2021.05.024
  %X Despite thousands of reported patients with pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative linkage to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pernio in uninfected children is associated with monogenic disorders of excessive IFN-1 immunity, whereas severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover, SARS-CoV-2 spike protein and robust IFN-1 response are seen in the skin of patients with pandemicassociated pernio, suggesting an excessive innate immune skin response to SARS-CoV-2. Understanding the pathophysiology of this phenomenon may elucidate the host mechanisms that drive a resilient immune response to SARS-CoV-2 and could produce relevant therapeutic targets.
  

• 1.

  Zhong, W., Danielsson, H., Tebani, A., Karlsson, M. J., Elfvin, A., Hellgren, G., Brusselaers, N., Brodin, P., Hellström, A., Fagerberg, L., and Uhlén, M. (2020) Dramatic changes in blood protein levels during the first week of life in extremely preterm infants, Pediatric Research.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Preterm birth and its complications are the primary cause of death among children under the age of 5. Among the survivors, morbidity both perinatally and later in life is common. The dawn of novel technical platforms for comprehensive and sensitive analysis of protein profiles in blood has opened up new possibilities to study both health and disease with significant clinical accuracy, here used to study the preterm infant and the physiological changes of the transition from intrauterine to extrauterine life.

  @article{zhong2020dramatic,
  abstract = {Preterm birth and its complications are the primary cause of death among children under the age of 5. Among the survivors, morbidity both perinatally and later in life is common. The dawn of novel technical platforms for comprehensive and sensitive analysis of protein profiles in blood has opened up new possibilities to study both health and disease with significant clinical accuracy, here used to study the preterm infant and the physiological changes of the transition from intrauterine to extrauterine life.},
  author = {Zhong, Wen and Danielsson, Hanna and Tebani, Abdellah and Karlsson, Max J. and Elfvin, Anders and Hellgren, Gunnel and Brusselaers, Nele and Brodin, Petter and Hellström, Ann and Fagerberg, Linn and Uhlén, Mathias},
  journal = {Pediatric Research},
  keywords = {Paediatric},
  title = {Dramatic changes in blood protein levels during the first week of life in extremely preterm infants},
  year = 2020
  }
  

  %0 Journal Article
  %1 zhong2020dramatic
  %A Zhong, Wen
  %A Danielsson, Hanna
  %A Tebani, Abdellah
  %A Karlsson, Max J.
  %A Elfvin, Anders
  %A Hellgren, Gunnel
  %A Brusselaers, Nele
  %A Brodin, Petter
  %A Hellström, Ann
  %A Fagerberg, Linn
  %A Uhlén, Mathias
  %D 2020
  %J Pediatric Research
  %R 10.1038/s41390-020-0912-8
  %T Dramatic changes in blood protein levels during the first week of life in extremely preterm infants
  %U https://doi.org/10.1038/s41390-020-0912-8
  %X Preterm birth and its complications are the primary cause of death among children under the age of 5. Among the survivors, morbidity both perinatally and later in life is common. The dawn of novel technical platforms for comprehensive and sensitive analysis of protein profiles in blood has opened up new possibilities to study both health and disease with significant clinical accuracy, here used to study the preterm infant and the physiological changes of the transition from intrauterine to extrauterine life.
  

• 1.

  Merid, S. K., Novoloaca, A., Sharp, G. C., Küpers, L. K., Kho, A. T., Roy, R., Gao, L., Annesi-Maesano, I., Jain, P., Plusquin, M., Kogevinas, M., Allard, C., Vehmeijer, F. O., Kazmi, N., Salas, L. A., Rezwan, F. I., Zhang, H., Sebert, S., Czamara, D., Rifas-Shiman, S. L., Melton, P. E., Lawlor, D. A., Pershagen, G., Breton, C. V., Huen, K., Baiz, N., Gagliardi, L., Nawrot, T. S., Corpeleijn, E., Perron, P., Duijts, L., Nohr, E. A., Bustamante, M., Ewart, S. L., Karmaus, W., Zhao, S., Page, C. M., Herceg, Z., Jarvelin, M.-R., Lahti, J., Baccarelli, A. A., Anderson, D., Kachroo, P., Relton, C. L., Bergström, A., Eskenazi, B., Soomro, M. H., Vineis, P., Snieder, H., Bouchard, L., Jaddoe, V. W., Sørensen, T. I. A., Vrijheid, M., Arshad, S. H., Holloway, J. W., Håberg, S. E., Magnus, P., Dwyer, T., Binder, E. B., DeMeo, D. L., Vonk, J. M., Newnham, J., Tantisira, K. G., Kull, I., Wiemels, J. L., Heude, B., Sunyer, J., Nystad, W., Munthe-Kaas, M. C., Räikkönen, K., Oken, E., Huang, R.-C., Weiss, S. T., Antó, J. M., Bousquet, J., Kumar, A., Söderhäll, C., Almqvist, C., Cardenas, A., Gruzieva, O., Xu, C.-J., Reese, S. E., Kere, J., Brodin, P., Solomon, O., Wielscher, M., Holland, N., Ghantous, A., Hivert, M.-F., Felix, J. F., Koppelman, G. H., London, S. J., and Melén, E. (2020) Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age., Genome medicine 12, 25.

  AbstractBibTeXEndNoteDOIBibSonomy

  BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

  @article{noauthororeditor,
  abstract = {BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.},
  author = {Merid, Simon Kebede and Novoloaca, Alexei and Sharp, Gemma C and Küpers, Leanne K and Kho, Alvin T and Roy, Ritu and Gao, Lu and Annesi-Maesano, Isabella and Jain, Pooja and Plusquin, Michelle and Kogevinas, Manolis and Allard, Catherine and Vehmeijer, Florianne O and Kazmi, Nabila and Salas, Lucas A and Rezwan, Faisal I and Zhang, Hongmei and Sebert, Sylvain and Czamara, Darina and Rifas-Shiman, Sheryl L and Melton, Phillip E and Lawlor, Debbie A. and Pershagen, Göran and Breton, Carrie V and Huen, Karen and Baiz, Nour and Gagliardi, Luigi and Nawrot, Tim S and Corpeleijn, Eva and Perron, Patrice and Duijts, Liesbeth and Nohr, Ellen Aagaard and Bustamante, Mariona and Ewart, Susan L and Karmaus, Wilfried and Zhao, Shanshan and Page, Christian M and Herceg, Zdenko and Jarvelin, Marjo-Riitta and Lahti, Jari and Baccarelli, Andrea A. and Anderson, Denise and Kachroo, Priyadarshini and Relton, Caroline L and Bergström, Anna and Eskenazi, Brenda and Soomro, Munawar Hussain and Vineis, Paolo and Snieder, Harold and Bouchard, Luigi and Jaddoe, Vincent W and Sørensen, Thorkild I. A and Vrijheid, Martine and Arshad, S. Hasan and Holloway, John W and Håberg, Siri E and Magnus, Per and Dwyer, Terence and Binder, Elisabeth B and DeMeo, Dawn L and Vonk, Judith M and Newnham, John and Tantisira, Kelan G and Kull, Inger and Wiemels, Joseph L and Heude, Barbara and Sunyer, Jordi and Nystad, Wenche and Munthe-Kaas, Monica C and Räikkönen, Katri and Oken, Emily and Huang, Rae-Chi and Weiss, Scott T and Antó, Josep Maria and Bousquet, Jean and Kumar, Ashish and Söderhäll, Cilla and Almqvist, Catarina and Cardenas, Andres and Gruzieva, Olena and Xu, Cheng-Jian and Reese, Sarah E and Kere, Juha and Brodin, Petter and Solomon, Olivia and Wielscher, Matthias and Holland, Nina and Ghantous, Akram and Hivert, Marie-France and Felix, Janine F and Koppelman, Gerard H and London, Stephanie J and Melén, Erik},
  journal = {Genome medicine},
  keywords = {Newborns},
  number = 1,
  pages = 25,
  title = {Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age.},
  volume = 12,
  year = 2020
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Merid, Simon Kebede
  %A Novoloaca, Alexei
  %A Sharp, Gemma C
  %A Küpers, Leanne K
  %A Kho, Alvin T
  %A Roy, Ritu
  %A Gao, Lu
  %A Annesi-Maesano, Isabella
  %A Jain, Pooja
  %A Plusquin, Michelle
  %A Kogevinas, Manolis
  %A Allard, Catherine
  %A Vehmeijer, Florianne O
  %A Kazmi, Nabila
  %A Salas, Lucas A
  %A Rezwan, Faisal I
  %A Zhang, Hongmei
  %A Sebert, Sylvain
  %A Czamara, Darina
  %A Rifas-Shiman, Sheryl L
  %A Melton, Phillip E
  %A Lawlor, Debbie A.
  %A Pershagen, Göran
  %A Breton, Carrie V
  %A Huen, Karen
  %A Baiz, Nour
  %A Gagliardi, Luigi
  %A Nawrot, Tim S
  %A Corpeleijn, Eva
  %A Perron, Patrice
  %A Duijts, Liesbeth
  %A Nohr, Ellen Aagaard
  %A Bustamante, Mariona
  %A Ewart, Susan L
  %A Karmaus, Wilfried
  %A Zhao, Shanshan
  %A Page, Christian M
  %A Herceg, Zdenko
  %A Jarvelin, Marjo-Riitta
  %A Lahti, Jari
  %A Baccarelli, Andrea A.
  %A Anderson, Denise
  %A Kachroo, Priyadarshini
  %A Relton, Caroline L
  %A Bergström, Anna
  %A Eskenazi, Brenda
  %A Soomro, Munawar Hussain
  %A Vineis, Paolo
  %A Snieder, Harold
  %A Bouchard, Luigi
  %A Jaddoe, Vincent W
  %A Sørensen, Thorkild I. A
  %A Vrijheid, Martine
  %A Arshad, S. Hasan
  %A Holloway, John W
  %A Håberg, Siri E
  %A Magnus, Per
  %A Dwyer, Terence
  %A Binder, Elisabeth B
  %A DeMeo, Dawn L
  %A Vonk, Judith M
  %A Newnham, John
  %A Tantisira, Kelan G
  %A Kull, Inger
  %A Wiemels, Joseph L
  %A Heude, Barbara
  %A Sunyer, Jordi
  %A Nystad, Wenche
  %A Munthe-Kaas, Monica C
  %A Räikkönen, Katri
  %A Oken, Emily
  %A Huang, Rae-Chi
  %A Weiss, Scott T
  %A Antó, Josep Maria
  %A Bousquet, Jean
  %A Kumar, Ashish
  %A Söderhäll, Cilla
  %A Almqvist, Catarina
  %A Cardenas, Andres
  %A Gruzieva, Olena
  %A Xu, Cheng-Jian
  %A Reese, Sarah E
  %A Kere, Juha
  %A Brodin, Petter
  %A Solomon, Olivia
  %A Wielscher, Matthias
  %A Holland, Nina
  %A Ghantous, Akram
  %A Hivert, Marie-France
  %A Felix, Janine F
  %A Koppelman, Gerard H
  %A London, Stephanie J
  %A Melén, Erik
  %D 2020
  %J Genome medicine
  %N 1
  %P 25
  %R 10.1186/s13073-020-0716-9
  %T Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age.
  %V 12
  %X BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
  

• 1.

  Consiglio, C. R., and Brodin, P. (2020) Stressful Beginnings with Long-Term Consequences, Cell 180, 820–821.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Early-life stress can have long-term health consequences, but the mechanisms of this are unknown. In this issue of Cell, Hong et al. demonstrate one such mechanism linking perinatal corticosteroid exposure to reduced CD8+ T cell function later in life and impaired anti-cancer and anti-bacterial immune responses.

  @article{CONSIGLIO2020820,
  abstract = {Early-life stress can have long-term health consequences, but the mechanisms of this are unknown. In this issue of Cell, Hong et al. demonstrate one such mechanism linking perinatal corticosteroid exposure to reduced CD8+ T cell function later in life and impaired anti-cancer and anti-bacterial immune responses.},
  author = {Consiglio, Camila Rosat and Brodin, Petter},
  journal = {Cell},
  keywords = {Neonatal},
  number = 5,
  pages = {820 - 821},
  title = {Stressful Beginnings with Long-Term Consequences},
  volume = 180,
  year = 2020
  }
  

  %0 Journal Article
  %1 CONSIGLIO2020820
  %A Consiglio, Camila Rosat
  %A Brodin, Petter
  %D 2020
  %J Cell
  %N 5
  %P 820 - 821
  %R https://doi.org/10.1016/j.cell.2020.02.021
  %T Stressful Beginnings with Long-Term Consequences
  %U http://www.sciencedirect.com/science/article/pii/S0092867420301653
  %V 180
  %X Early-life stress can have long-term health consequences, but the mechanisms of this are unknown. In this issue of Cell, Hong et al. demonstrate one such mechanism linking perinatal corticosteroid exposure to reduced CD8+ T cell function later in life and impaired anti-cancer and anti-bacterial immune responses.
  

• 1.

  Brodin, P. (2020) New approaches to the study of immune responses in humans, Human Genetics.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  The human immune system consists of multiple, layered mechanisms of sensing and responding to cellular stress, infection and tissue damage to ensure defense from pathogens, maintenance of tissue homeostasis, and the integrity of the holobiont. Every single cell in the body has a role to play, but a few dozen, specialized white blood cells are particularly important in this respect. Understanding the overall state of this multifaceted system in a single individual is challenging, and we are only beginning to do this across populations of individuals, to understand the vast range of inter-individual variation, and the influences of genes and environmental factors that collectively shape the immune system in a given individual. We are also only beginning to understand the changes occurring within this system over time, and how this relates to health and disease susceptibility. Several technological breakthroughs in recent years have enabled these developments and the emergence of a new, complementary approach to studying human immune systems, namely systems immunology. In this paradigm, the focus is shifted from the understanding of individual immune system components and their mechanisms of action, towards analyses of cell--cell interactions, and mechanisms of coordination and regulation within the human immune system.

  @article{Brodin2020,
  abstract = {The human immune system consists of multiple, layered mechanisms of sensing and responding to cellular stress, infection and tissue damage to ensure defense from pathogens, maintenance of tissue homeostasis, and the integrity of the holobiont. Every single cell in the body has a role to play, but a few dozen, specialized white blood cells are particularly important in this respect. Understanding the overall state of this multifaceted system in a single individual is challenging, and we are only beginning to do this across populations of individuals, to understand the vast range of inter-individual variation, and the influences of genes and environmental factors that collectively shape the immune system in a given individual. We are also only beginning to understand the changes occurring within this system over time, and how this relates to health and disease susceptibility. Several technological breakthroughs in recent years have enabled these developments and the emergence of a new, complementary approach to studying human immune systems, namely systems immunology. In this paradigm, the focus is shifted from the understanding of individual immune system components and their mechanisms of action, towards analyses of cell--cell interactions, and mechanisms of coordination and regulation within the human immune system.},
  author = {Brodin, Petter},
  journal = {Human Genetics},
  keywords = {immune response},
  month = {feb},
  title = {New approaches to the study of immune responses in humans},
  year = 2020
  }
  

  %0 Journal Article
  %1 Brodin2020
  %A Brodin, Petter
  %D 2020
  %J Human Genetics
  %R 10.1007/s00439-020-02129-3
  %T New approaches to the study of immune responses in humans
  %U https://doi.org/10.1007/s00439-020-02129-3
  %X The human immune system consists of multiple, layered mechanisms of sensing and responding to cellular stress, infection and tissue damage to ensure defense from pathogens, maintenance of tissue homeostasis, and the integrity of the holobiont. Every single cell in the body has a role to play, but a few dozen, specialized white blood cells are particularly important in this respect. Understanding the overall state of this multifaceted system in a single individual is challenging, and we are only beginning to do this across populations of individuals, to understand the vast range of inter-individual variation, and the influences of genes and environmental factors that collectively shape the immune system in a given individual. We are also only beginning to understand the changes occurring within this system over time, and how this relates to health and disease susceptibility. Several technological breakthroughs in recent years have enabled these developments and the emergence of a new, complementary approach to studying human immune systems, namely systems immunology. In this paradigm, the focus is shifted from the understanding of individual immune system components and their mechanisms of action, towards analyses of cell--cell interactions, and mechanisms of coordination and regulation within the human immune system.
  

• 1.

  Rodriguez, L. S., Pou, C., Lakshmikanth, T., Zhang, J., Mugabo, C. H., Wang, J., Mikes, J., Olin, A., Chen, Y., Rorbach, J., Juto, J.-E., Li, T. Q., Julin, P., and Brodin, P. (2020) Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance, bioRxiv, Cold Spring Harbor Laboratory.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and induce a sustainable, ~30% reduction in overall symptom scores after eight weeks of treatment. By performing longitudinal, systems-level monitoring of the blood immune system in these patients, we uncover chronic immune activation in ME, as well as immunological correlates of improvement that center around the IL-17 axis, gut-homing immune cells and reduced inflammation. The mechanisms of symptom relief remains to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We wish for these results to bring some hope to patients suffering from ME and inspire researchers to help test our new hypothesis that ME is a condition caused by a failure of inducing disease tolerance upon infection and persistent immune activation.

  @article{Rodriguez2020.02.20.958249,
  abstract = {Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and induce a sustainable, ~30% reduction in overall symptom scores after eight weeks of treatment. By performing longitudinal, systems-level monitoring of the blood immune system in these patients, we uncover chronic immune activation in ME, as well as immunological correlates of improvement that center around the IL-17 axis, gut-homing immune cells and reduced inflammation. The mechanisms of symptom relief remains to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We wish for these results to bring some hope to patients suffering from ME and inspire researchers to help test our new hypothesis that ME is a condition caused by a failure of inducing disease tolerance upon infection and persistent immune activation.},
  author = {Rodriguez, Lucie S.T. and Pou, Christian and Lakshmikanth, Tadepally and Zhang, Jingdian and Mugabo, Constantin Habimana and Wang, Jun and Mikes, Jaromir and Olin, Axel and Chen, Yang and Rorbach, Joanna and Juto, Jan-Erik and Li, Tie Qiang and Julin, Per and Brodin, Petter},
  journal = {bioRxiv},
  keywords = {ME/CFS},
  publisher = {Cold Spring Harbor Laboratory},
  title = {Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance},
  year = 2020
  }
  

  %0 Journal Article
  %1 Rodriguez2020.02.20.958249
  %A Rodriguez, Lucie S.T.
  %A Pou, Christian
  %A Lakshmikanth, Tadepally
  %A Zhang, Jingdian
  %A Mugabo, Constantin Habimana
  %A Wang, Jun
  %A Mikes, Jaromir
  %A Olin, Axel
  %A Chen, Yang
  %A Rorbach, Joanna
  %A Juto, Jan-Erik
  %A Li, Tie Qiang
  %A Julin, Per
  %A Brodin, Petter
  %D 2020
  %I Cold Spring Harbor Laboratory
  %J bioRxiv
  %R 10.1101/2020.02.20.958249
  %T Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance
  %U https://www.biorxiv.org/content/early/2020/02/21/2020.02.20.958249
  %X Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and induce a sustainable, ~30% reduction in overall symptom scores after eight weeks of treatment. By performing longitudinal, systems-level monitoring of the blood immune system in these patients, we uncover chronic immune activation in ME, as well as immunological correlates of improvement that center around the IL-17 axis, gut-homing immune cells and reduced inflammation. The mechanisms of symptom relief remains to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We wish for these results to bring some hope to patients suffering from ME and inspire researchers to help test our new hypothesis that ME is a condition caused by a failure of inducing disease tolerance upon infection and persistent immune activation.
  

• 1.

  Lakshmikanth, T., Muhammad, S. A., Olin, A., Chen, Y., Mikes, J., Fagerberg, L., Gummesson, A., Bergström, G., Uhlen, M., and Brodin, P. (2020) Human immune system variation during one year, bioRxiv, Cold Spring Harbor Laboratory.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components, and the inference of global regulatory principles. Here we present a longitudinal, systems-level analysis in 99 healthy adults, 50 to 65 years of age and sampled every 3rd month during one year. We describe the structure of inter-individual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited markers of poor metabolic health suggestive of a functional link between metabolic and immunologic homeostatic regulation.HIGHLIGHTS Longitudinal variation in immune cell composition during one yearInter-individual variation can be described along a principal curveImmune cell and protein relationships are inferredVariability over time is an individual feature correlating with markers of poor metabolic health

  @article{Lakshmikanth2020.01.22.915025,
  abstract = {The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components, and the inference of global regulatory principles. Here we present a longitudinal, systems-level analysis in 99 healthy adults, 50 to 65 years of age and sampled every 3rd month during one year. We describe the structure of inter-individual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited markers of poor metabolic health suggestive of a functional link between metabolic and immunologic homeostatic regulation.HIGHLIGHTS Longitudinal variation in immune cell composition during one yearInter-individual variation can be described along a principal curveImmune cell and protein relationships are inferredVariability over time is an individual feature correlating with markers of poor metabolic health},
  author = {Lakshmikanth, Tadepally and Muhammad, Sayyed Auwn and Olin, Axel and Chen, Yang and Mikes, Jaromir and Fagerberg, Linn and Gummesson, Anders and Bergström, Göran and Uhlen, Mathias and Brodin, Petter},
  journal = {bioRxiv},
  keywords = {Human immune variation},
  publisher = {Cold Spring Harbor Laboratory},
  title = {Human immune system variation during one year},
  year = 2020
  }
  

  %0 Journal Article
  %1 Lakshmikanth2020.01.22.915025
  %A Lakshmikanth, Tadepally
  %A Muhammad, Sayyed Auwn
  %A Olin, Axel
  %A Chen, Yang
  %A Mikes, Jaromir
  %A Fagerberg, Linn
  %A Gummesson, Anders
  %A Bergström, Göran
  %A Uhlen, Mathias
  %A Brodin, Petter
  %D 2020
  %I Cold Spring Harbor Laboratory
  %J bioRxiv
  %R 10.1101/2020.01.22.915025
  %T Human immune system variation during one year
  %U https://www.biorxiv.org/content/early/2020/01/23/2020.01.22.915025
  %X The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components, and the inference of global regulatory principles. Here we present a longitudinal, systems-level analysis in 99 healthy adults, 50 to 65 years of age and sampled every 3rd month during one year. We describe the structure of inter-individual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited markers of poor metabolic health suggestive of a functional link between metabolic and immunologic homeostatic regulation.HIGHLIGHTS Longitudinal variation in immune cell composition during one yearInter-individual variation can be described along a principal curveImmune cell and protein relationships are inferredVariability over time is an individual feature correlating with markers of poor metabolic health
  

• 1.

  Brodin, P. (2020) Why is COVID-19 so mild in children?, Acta pædiatrica.

  AbstractBibTeXEndNoteDOIBibSonomy

  There is an urgent need to understand why the course of the coronavirus that started in late 2019 (COVID-19) is affecting different groups of individuals with varying severity during the ongoing global pandemic. Greater knowledge of the disease, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), will help us to prioritise our limited health resources. Because the virus is new, and no vaccine is yet available, everyone is naïve and susceptible to being infected with SARS-CoV2. The virus will continue to spread until an effective vaccine exists or sufficient members of our global population have been infected to establish herd immunity. At the moment, the best way to minimize loss of life and severe cases requiring intensive care is to try and shelter vulnerable groups of individuals and slow down the spread of the virus.

  @article{noauthororeditor,
  abstract = {There is an urgent need to understand why the course of the coronavirus that started in late 2019 (COVID-19) is affecting different groups of individuals with varying severity during the ongoing global pandemic. Greater knowledge of the disease, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), will help us to prioritise our limited health resources. Because the virus is new, and no vaccine is yet available, everyone is naïve and susceptible to being infected with SARS-CoV2. The virus will continue to spread until an effective vaccine exists or sufficient members of our global population have been infected to establish herd immunity. At the moment, the best way to minimize loss of life and severe cases requiring intensive care is to try and shelter vulnerable groups of individuals and slow down the spread of the virus.},
  author = {Brodin, Petter},
  journal = {Acta pædiatrica},
  keywords = {Covid-19},
  month = {March},
  title = {Why is COVID-19 so mild in children?},
  year = 2020
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Brodin, Petter
  %D 2020
  %J Acta pædiatrica
  %R 10.1111/apa.15271
  %T Why is COVID-19 so mild in children?
  %X There is an urgent need to understand why the course of the coronavirus that started in late 2019 (COVID-19) is affecting different groups of individuals with varying severity during the ongoing global pandemic. Greater knowledge of the disease, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), will help us to prioritise our limited health resources. Because the virus is new, and no vaccine is yet available, everyone is naïve and susceptible to being infected with SARS-CoV2. The virus will continue to spread until an effective vaccine exists or sufficient members of our global population have been infected to establish herd immunity. At the moment, the best way to minimize loss of life and severe cases requiring intensive care is to try and shelter vulnerable groups of individuals and slow down the spread of the virus.
  

• 1.

  Brodin, P., and Quintana-Murci, L. (2020) Editorial overview: Evolutionary and systems immunology – methods to understand human immune system variation, Current Opinion in Immunology 65, iv.

  URLBibTeXEndNoteDOIBibSonomy

  @article{BRODIN2020iv,
  author = {Brodin, Petter and Quintana-Murci, Lluis},
  journal = {Current Opinion in Immunology},
  keywords = {Immunology Systems},
  note = {Vaccines • Special Section on Evolutionary and systems immunology},
  pages = {iv},
  title = {Editorial overview: Evolutionary and systems immunology – methods to understand human immune system variation},
  volume = 65,
  year = 2020
  }
  

  %0 Journal Article
  %1 BRODIN2020iv
  %A Brodin, Petter
  %A Quintana-Murci, Lluis
  %D 2020
  %J Current Opinion in Immunology
  %P iv
  %R https://doi.org/10.1016/j.coi.2020.11.001
  %T Editorial overview: Evolutionary and systems immunology – methods to understand human immune system variation
  %U https://www.sciencedirect.com/science/article/pii/S0952791520301151
  %V 65
  

• 1.

  Brodin, P. (2020) Technologies for assessing vaccine responses in the very young, Current Opinion in Immunology 65, 28–31.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Many vaccines are administered to young children in order to prevent infectious diseases early in life. At the same time, most of these vaccines are not developed specifically with the immune system of young children in mind and our understanding of how newborn immune systems differ from adult counterparts is incomplete. The main reason for this lack of understanding stems from the ethical and logistical difficulties in obtaining samples from young children as well as the challenges associated with the small volume samples available. Here I review some recent developments made in this field and discuss their implications for studying vaccine responses in young children and developing better vaccines, tailored to this important population of susceptible individuals in the future.

  @article{BRODIN202028,
  abstract = {Many vaccines are administered to young children in order to prevent infectious diseases early in life. At the same time, most of these vaccines are not developed specifically with the immune system of young children in mind and our understanding of how newborn immune systems differ from adult counterparts is incomplete. The main reason for this lack of understanding stems from the ethical and logistical difficulties in obtaining samples from young children as well as the challenges associated with the small volume samples available. Here I review some recent developments made in this field and discuss their implications for studying vaccine responses in young children and developing better vaccines, tailored to this important population of susceptible individuals in the future.},
  author = {Brodin, Petter},
  journal = {Current Opinion in Immunology},
  keywords = {Vaccines},
  pages = {28 - 31},
  title = {Technologies for assessing vaccine responses in the very young},
  volume = 65,
  year = 2020
  }
  

  %0 Journal Article
  %1 BRODIN202028
  %A Brodin, Petter
  %D 2020
  %J Current Opinion in Immunology
  %P 28 - 31
  %R https://doi.org/10.1016/j.coi.2020.03.011
  %T Technologies for assessing vaccine responses in the very young
  %U http://www.sciencedirect.com/science/article/pii/S0952791520300340
  %V 65
  %X Many vaccines are administered to young children in order to prevent infectious diseases early in life. At the same time, most of these vaccines are not developed specifically with the immune system of young children in mind and our understanding of how newborn immune systems differ from adult counterparts is incomplete. The main reason for this lack of understanding stems from the ethical and logistical difficulties in obtaining samples from young children as well as the challenges associated with the small volume samples available. Here I review some recent developments made in this field and discuss their implications for studying vaccine responses in young children and developing better vaccines, tailored to this important population of susceptible individuals in the future.
  

• 1.

  Casanova, J.-L., and Su, H. C. on behalf of the C. H. G. E. (2020) A global effort to define the human genetics of protective immunity to SARS-CoV-2 infection, Cell.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers – individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease – presents a unique opportunity to reveal human genetic determinants of infection and disease.

  @article{CASANOVA2020,
  abstract = {SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers – individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease – presents a unique opportunity to reveal human genetic determinants of infection and disease.},
  author = {Casanova, Jean-Laurent and Su, Helen C. on behalf of the COVID Human Genetic Effort},
  journal = {Cell},
  keywords = {SARS-Cov-2},
  title = {A global effort to define the human genetics of protective immunity to SARS-CoV-2 infection},
  year = 2020
  }
  

  %0 Journal Article
  %1 CASANOVA2020
  %A Casanova, Jean-Laurent
  %A Su, Helen C. on behalf of the COVID Human Genetic Effort
  %D 2020
  %J Cell
  %R https://doi.org/10.1016/j.cell.2020.05.016
  %T A global effort to define the human genetics of protective immunity to SARS-CoV-2 infection
  %U http://www.sciencedirect.com/science/article/pii/S0092867420306115
  %X SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers – individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease – presents a unique opportunity to reveal human genetic determinants of infection and disease.
  

• 1.

  Lakshmikanth, T., Muhammad, S. A., Olin, A., Chen, Y., Mikes, J., Fagerberg, L., Gummesson, A., Bergström, G., Uhlen, M., and Brodin, P. (2020) Human Immune System Variation during 1 Year, Cell Reports, Elsevier 32.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components and the inference of global regulatory principles. Here, we present a longitudinal, systems-level analysis in 99 healthy adults 50 to 65 years of age and sampled every third month for 1 year. We describe the structure of interindividual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited differences in markers of metabolic health suggestive of a possible link between metabolic and immunologic homeostatic regulation.

  @article{lakshmikanth2020human,
  abstract = {The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components and the inference of global regulatory principles. Here, we present a longitudinal, systems-level analysis in 99 healthy adults 50 to 65 years of age and sampled every third month for 1 year. We describe the structure of interindividual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited differences in markers of metabolic health suggestive of a possible link between metabolic and immunologic homeostatic regulation.},
  author = {Lakshmikanth, Tadepally and Muhammad, Sayyed Auwn and Olin, Axel and Chen, Yang and Mikes, Jaromir and Fagerberg, Linn and Gummesson, Anders and Bergström, Göran and Uhlen, Mathias and Brodin, Petter},
  booktitle = {Cell Reports},
  journal = {Cell Reports},
  keywords = {Human immune variation},
  month = {jul},
  number = 3,
  publisher = {Elsevier},
  title = {Human Immune System Variation during 1 Year},
  volume = 32,
  year = 2020
  }
  

  %0 Journal Article
  %1 lakshmikanth2020human
  %A Lakshmikanth, Tadepally
  %A Muhammad, Sayyed Auwn
  %A Olin, Axel
  %A Chen, Yang
  %A Mikes, Jaromir
  %A Fagerberg, Linn
  %A Gummesson, Anders
  %A Bergström, Göran
  %A Uhlen, Mathias
  %A Brodin, Petter
  %B Cell Reports
  %D 2020
  %I Elsevier
  %J Cell Reports
  %N 3
  %R 10.1016/j.celrep.2020.107923
  %T Human Immune System Variation during 1 Year
  %U https://doi.org/10.1016/j.celrep.2020.107923
  %V 32
  %X The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components and the inference of global regulatory principles. Here, we present a longitudinal, systems-level analysis in 99 healthy adults 50 to 65 years of age and sampled every third month for 1 year. We describe the structure of interindividual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited differences in markers of metabolic health suggestive of a possible link between metabolic and immunologic homeostatic regulation.
  

• 1.

  Petkov, S., Bekele, Y., Lakshmikanth, T., Hejdeman, B., Zazzi, M., Brodin, P., and Chiodi, F. (2020) High CD45 expression of CD8+ and CD4+ T cells correlates with the size of HIV-1 reservoir in blood, Scientific Reports 10, 20425-.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Using mass cytometry, we investigated the expression of 28 markers on CD8+ and CD4+ T cells from HIV-1 infected patients with a variable size of HIV-1 reservoir defined as high (HR) and low (LR) reservoir; we aimed at identifying phenotypic associations of T cells with size of HIV-1 reservoir. We showed that the frequency of CD45+ CD8+ and CD4+ T cells was directly proportional to the size of HIV-1 reservoir; HR patients had a significantly larger frequency of blood CD45high T cells and higher CD45 expression on both CD8+ and CD4+ T cells. CD45 is a receptor-type protein tyrosine phosphatase essential in TCR signaling. Functional and phenotypical analysis of CD45high cells revealed that they express activation and proliferation markers (CD38 + HLA-DR + and Ki-67) and produce cytokines upon in vitro activation. CD45high T cells also expressed high levels of immune check-point PD-1. Our results link CD45 expression on T cells to HIV-1 reservoir; PD-1 expression on CD45high T cells may contribute to their exhaustion.

  @article{petkov2020expression,
  abstract = {Using mass cytometry, we investigated the expression of 28 markers on CD8+ and CD4+ T cells from HIV-1 infected patients with a variable size of HIV-1 reservoir defined as high (HR) and low (LR) reservoir; we aimed at identifying phenotypic associations of T cells with size of HIV-1 reservoir. We showed that the frequency of CD45+ CD8+ and CD4+ T cells was directly proportional to the size of HIV-1 reservoir; HR patients had a significantly larger frequency of blood CD45high T cells and higher CD45 expression on both CD8+ and CD4+ T cells. CD45 is a receptor-type protein tyrosine phosphatase essential in TCR signaling. Functional and phenotypical analysis of CD45high cells revealed that they express activation and proliferation markers (CD38 + HLA-DR + and Ki-67) and produce cytokines upon in vitro activation. CD45high T cells also expressed high levels of immune check-point PD-1. Our results link CD45 expression on T cells to HIV-1 reservoir; PD-1 expression on CD45high T cells may contribute to their exhaustion.},
  author = {Petkov, Stefan and Bekele, Yonas and Lakshmikanth, Tadepally and Hejdeman, Bo and Zazzi, Maurizio and Brodin, Petter and Chiodi, Francesca},
  journal = {Scientific Reports},
  keywords = {cd4 cd8},
  number = 1,
  pages = {20425--},
  title = {High CD45 expression of CD8+ and CD4+ T cells correlates with the size of HIV-1 reservoir in blood},
  volume = 10,
  year = 2020
  }
  

  %0 Journal Article
  %1 petkov2020expression
  %A Petkov, Stefan
  %A Bekele, Yonas
  %A Lakshmikanth, Tadepally
  %A Hejdeman, Bo
  %A Zazzi, Maurizio
  %A Brodin, Petter
  %A Chiodi, Francesca
  %D 2020
  %J Scientific Reports
  %N 1
  %P 20425--
  %R 10.1038/s41598-020-77433-z
  %T High CD45 expression of CD8+ and CD4+ T cells correlates with the size of HIV-1 reservoir in blood
  %U https://doi.org/10.1038/s41598-020-77433-z
  %V 10
  %X Using mass cytometry, we investigated the expression of 28 markers on CD8+ and CD4+ T cells from HIV-1 infected patients with a variable size of HIV-1 reservoir defined as high (HR) and low (LR) reservoir; we aimed at identifying phenotypic associations of T cells with size of HIV-1 reservoir. We showed that the frequency of CD45+ CD8+ and CD4+ T cells was directly proportional to the size of HIV-1 reservoir; HR patients had a significantly larger frequency of blood CD45high T cells and higher CD45 expression on both CD8+ and CD4+ T cells. CD45 is a receptor-type protein tyrosine phosphatase essential in TCR signaling. Functional and phenotypical analysis of CD45high cells revealed that they express activation and proliferation markers (CD38 + HLA-DR + and Ki-67) and produce cytokines upon in vitro activation. CD45high T cells also expressed high levels of immune check-point PD-1. Our results link CD45 expression on T cells to HIV-1 reservoir; PD-1 expression on CD45high T cells may contribute to their exhaustion.
  

• 1.

  Rodriguez, L., Pekkarinen, P. T., Lakshmikanth, T., Tan, Z., Consiglio, C. R., Pou, C., Chen, Y., Mugabo, C. H., Nguyen, N. A., Nowlan, K., Strandin, T., Levanov, L., Mikes, J., Wang, J., Kantele, A., Hepojoki, J., Vapalahti, O., Heinonen, S., Kekäläinen, E., and Brodin, P. (2020) Systems-level immunomonitoring from acute to recovery phase of severe COVID-19, Cell Reports Medicine, Elsevier.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Severe disease of SARS-CoV2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses required to capture cellular interactions. Here we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFN? ? Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.

  @article{rodriguezsystemslevel,
  abstract = {Severe disease of SARS-CoV2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses required to capture cellular interactions. Here we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFN? ? Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.},
  author = {Rodriguez, Lucie and Pekkarinen, Pirkka T. and Lakshmikanth, Tadepally and Tan, Ziyang and Consiglio, Camila Rosat and Pou, Christian and Chen, Yang and Mugabo, Constantin Habimana and Nguyen, Ngoc Anh and Nowlan, Kirsten and Strandin, Tomas and Levanov, Lev and Mikes, Jaromir and Wang, Jun and Kantele, Anu and Hepojoki, Jussi and Vapalahti, Olli and Heinonen, Santtu and Kekäläinen, Eliisa and Brodin, Petter},
  booktitle = {Cell Reports Medicine},
  journal = {Cell Reports Medicine},
  keywords = {Covid-19},
  publisher = {Elsevier},
  title = {Systems-level immunomonitoring from acute to recovery phase of severe COVID-19},
  year = 2020
  }
  

  %0 Journal Article
  %1 rodriguezsystemslevel
  %A Rodriguez, Lucie
  %A Pekkarinen, Pirkka T.
  %A Lakshmikanth, Tadepally
  %A Tan, Ziyang
  %A Consiglio, Camila Rosat
  %A Pou, Christian
  %A Chen, Yang
  %A Mugabo, Constantin Habimana
  %A Nguyen, Ngoc Anh
  %A Nowlan, Kirsten
  %A Strandin, Tomas
  %A Levanov, Lev
  %A Mikes, Jaromir
  %A Wang, Jun
  %A Kantele, Anu
  %A Hepojoki, Jussi
  %A Vapalahti, Olli
  %A Heinonen, Santtu
  %A Kekäläinen, Eliisa
  %A Brodin, Petter
  %B Cell Reports Medicine
  %D 2020
  %I Elsevier
  %J Cell Reports Medicine
  %R 10.1016/j.xcrm.2020.100078
  %T Systems-level immunomonitoring from acute to recovery phase of severe COVID-19
  %U https://doi.org/10.1016/j.xcrm.2020.100078
  %X Severe disease of SARS-CoV2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses required to capture cellular interactions. Here we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFN? ? Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.
  

• 1.

  Rodriguez, L., and Brodin, P. (2020) Unraveling the Immune Response in Severe COVID-19, Journal of Clinical Immunology.

  URLBibTeXEndNoteDOIBibSonomy

  @article{Rodriguez2020,
  author = {Rodriguez, Lucie and Brodin, Petter},
  journal = {Journal of Clinical Immunology},
  keywords = {Covid-19},
  month = {aug},
  title = {Unraveling the Immune Response in Severe COVID-19},
  year = 2020
  }
  

  %0 Journal Article
  %1 Rodriguez2020
  %A Rodriguez, Lucie
  %A Brodin, Petter
  %D 2020
  %J Journal of Clinical Immunology
  %R 10.1007/s10875-020-00849-9
  %T Unraveling the Immune Response in Severe COVID-19
  %U https://doi.org/10.1007/s10875-020-00849-9
  

• 1.

  Consiglio, C. R., Cotugno, N., Sardh, F., Pou, C., Amodio, D., Rodriguez, L., Tan, Z., Zicari, S., Ruggiero, A., Pascucci, G. R., Santilli, V., Campbell, T., Bryceson, Y., Eriksson, D., Wang, J., Marchesi, A., Lakshmikanth, T., Campana, A., Villani, A., Rossi, P., Landegren, N., Palma, P., and Brodin, P. (2020) The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19, Cell, Elsevier.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Hyperinflammation in MIS-C differs from that of acute COVID-19T-cell subsets discriminate Kawasaki disease patients from MIS-CIL-17A drives Kawasaki, but not MIS-C hyperinflammation.Global profiling reveals candidate autoantibodies with pathogenic potential

  @article{consiglioimmunology,
  abstract = {Hyperinflammation in MIS-C differs from that of acute COVID-19T-cell subsets discriminate Kawasaki disease patients from MIS-CIL-17A drives Kawasaki, but not MIS-C hyperinflammation.Global profiling reveals candidate autoantibodies with pathogenic potential},
  author = {Consiglio, Camila Rosat and Cotugno, Nicola and Sardh, Fabian and Pou, Christian and Amodio, Donato and Rodriguez, Lucie and Tan, Ziyang and Zicari, Sonia and Ruggiero, Alessandra and Pascucci, Giuseppe Rubens and Santilli, Veronica and Campbell, Tessa and Bryceson, Yenan and Eriksson, Daniel and Wang, Jun and Marchesi, Alessandra and Lakshmikanth, Tadepally and Campana, Andrea and Villani, Alberto and Rossi, Paolo and Landegren, Nils and Palma, Paolo and Brodin, Petter},
  booktitle = {Cell},
  journal = {Cell},
  keywords = {MIS-C},
  publisher = {Elsevier},
  title = {The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19},
  year = 2020
  }
  

  %0 Journal Article
  %1 consiglioimmunology
  %A Consiglio, Camila Rosat
  %A Cotugno, Nicola
  %A Sardh, Fabian
  %A Pou, Christian
  %A Amodio, Donato
  %A Rodriguez, Lucie
  %A Tan, Ziyang
  %A Zicari, Sonia
  %A Ruggiero, Alessandra
  %A Pascucci, Giuseppe Rubens
  %A Santilli, Veronica
  %A Campbell, Tessa
  %A Bryceson, Yenan
  %A Eriksson, Daniel
  %A Wang, Jun
  %A Marchesi, Alessandra
  %A Lakshmikanth, Tadepally
  %A Campana, Andrea
  %A Villani, Alberto
  %A Rossi, Paolo
  %A Landegren, Nils
  %A Palma, Paolo
  %A Brodin, Petter
  %B Cell
  %D 2020
  %I Elsevier
  %J Cell
  %R 10.1016/j.cell.2020.09.016
  %T The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19
  %U https://doi.org/10.1016/j.cell.2020.09.016
  %X Hyperinflammation in MIS-C differs from that of acute COVID-19T-cell subsets discriminate Kawasaki disease patients from MIS-CIL-17A drives Kawasaki, but not MIS-C hyperinflammation.Global profiling reveals candidate autoantibodies with pathogenic potential
  

• 1.

  Tebani, A., Gummesson, A., Zhong, W., Koistinen, I. S., Lakshmikanth, T., Olsson, L. M., Boulund, F., Neiman, M., Stenlund, H., Hellström, C., Karlsson, M. J., Arif, M., Dodig-Crnković, T., Mardinoglu, A., Lee, S., Zhang, C., Chen, Y., Olin, A., Mikes, J., Danielsson, H., von Feilitzen, K., Jansson, P.-A., Angerås, O., Huss, M., Kjellqvist, S., Odeberg, J., Edfors, F., Tremaroli, V., Forsström, B., Schwenk, J. M., Nilsson, P., Moritz, T., Bäckhed, F., Engstrand, L., Brodin, P., Bergström, G., Uhlen, M., and Fagerberg, L. (2020) Integration of molecular profiles in a longitudinal wellness profiling cohort, Nature Communications 11, 4487-.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.

  @article{tebani2020integration,
  abstract = {An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.},
  author = {Tebani, Abdellah and Gummesson, Anders and Zhong, Wen and Koistinen, Ina Schuppe and Lakshmikanth, Tadepally and Olsson, Lisa M. and Boulund, Fredrik and Neiman, Maja and Stenlund, Hans and Hellström, Cecilia and Karlsson, Max J. and Arif, Muhammad and Dodig-Crnković, Tea and Mardinoglu, Adil and Lee, Sunjae and Zhang, Cheng and Chen, Yang and Olin, Axel and Mikes, Jaromir and Danielsson, Hanna and von Feilitzen, Kalle and Jansson, Per-Anders and Angerås, Oskar and Huss, Mikael and Kjellqvist, Sanela and Odeberg, Jacob and Edfors, Fredrik and Tremaroli, Valentina and Forsström, Björn and Schwenk, Jochen M. and Nilsson, Peter and Moritz, Thomas and Bäckhed, Fredrik and Engstrand, Lars and Brodin, Petter and Bergström, Göran and Uhlen, Mathias and Fagerberg, Linn},
  journal = {Nature Communications},
  keywords = {SCAPIS},
  number = 1,
  pages = {4487--},
  title = {Integration of molecular profiles in a longitudinal wellness profiling cohort},
  volume = 11,
  year = 2020
  }
  

  %0 Journal Article
  %1 tebani2020integration
  %A Tebani, Abdellah
  %A Gummesson, Anders
  %A Zhong, Wen
  %A Koistinen, Ina Schuppe
  %A Lakshmikanth, Tadepally
  %A Olsson, Lisa M.
  %A Boulund, Fredrik
  %A Neiman, Maja
  %A Stenlund, Hans
  %A Hellström, Cecilia
  %A Karlsson, Max J.
  %A Arif, Muhammad
  %A Dodig-Crnković, Tea
  %A Mardinoglu, Adil
  %A Lee, Sunjae
  %A Zhang, Cheng
  %A Chen, Yang
  %A Olin, Axel
  %A Mikes, Jaromir
  %A Danielsson, Hanna
  %A von Feilitzen, Kalle
  %A Jansson, Per-Anders
  %A Angerås, Oskar
  %A Huss, Mikael
  %A Kjellqvist, Sanela
  %A Odeberg, Jacob
  %A Edfors, Fredrik
  %A Tremaroli, Valentina
  %A Forsström, Björn
  %A Schwenk, Jochen M.
  %A Nilsson, Peter
  %A Moritz, Thomas
  %A Bäckhed, Fredrik
  %A Engstrand, Lars
  %A Brodin, Petter
  %A Bergström, Göran
  %A Uhlen, Mathias
  %A Fagerberg, Linn
  %D 2020
  %J Nature Communications
  %N 1
  %P 4487--
  %R 10.1038/s41467-020-18148-7
  %T Integration of molecular profiles in a longitudinal wellness profiling cohort
  %U https://doi.org/10.1038/s41467-020-18148-7
  %V 11
  %X An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
  

• 1.

  Zhang, Q., Bastard, P., Bolze, A., Jouanguy, E., Zhang, S.-Y., Cobat, A., Notarangelo, L. D., Su, H. C., Abel, L., and Casanova, J.-L. (2020) Life-Threatening COVID-19: Defective Interferons Unleash Excessive Inflammation, Med, Elsevier 1, 14–20.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  The risk of life-threatening COVID-19 pneumonia increases sharply after 65 years of age, but other epidemiological risk factors, genetic or otherwise, are modest. Various rare monogenic inborn errors of type I interferons (IFNs) underlie critical disease, and neutralizing autoantibodies against type I IFNs account for at least 10% of critical cases.

  @article{zhang2020lifethreatening,
  abstract = {The risk of life-threatening COVID-19 pneumonia increases sharply after 65 years of age, but other epidemiological risk factors, genetic or otherwise, are modest. Various rare monogenic inborn errors of type I interferons (IFNs) underlie critical disease, and neutralizing autoantibodies against type I IFNs account for at least 10% of critical cases.},
  author = {Zhang, Qian and Bastard, Paul and Bolze, Alexandre and Jouanguy, Emmanuelle and Zhang, Shen-Ying and Cobat, Aurélie and Notarangelo, Luigi D. and Su, Helen C. and Abel, Laurent and Casanova, Jean-Laurent},
  booktitle = {Med},
  journal = {Med},
  keywords = {IFN},
  month = {dec},
  number = 1,
  pages = {14--20},
  publisher = {Elsevier},
  title = {Life-Threatening COVID-19: Defective Interferons Unleash Excessive Inflammation},
  volume = 1,
  year = 2020
  }
  

  %0 Journal Article
  %1 zhang2020lifethreatening
  %A Zhang, Qian
  %A Bastard, Paul
  %A Bolze, Alexandre
  %A Jouanguy, Emmanuelle
  %A Zhang, Shen-Ying
  %A Cobat, Aurélie
  %A Notarangelo, Luigi D.
  %A Su, Helen C.
  %A Abel, Laurent
  %A Casanova, Jean-Laurent
  %B Med
  %D 2020
  %I Elsevier
  %J Med
  %N 1
  %P 14--20
  %R 10.1016/j.medj.2020.12.001
  %T Life-Threatening COVID-19: Defective Interferons Unleash Excessive Inflammation
  %U https://doi.org/10.1016/j.medj.2020.12.001
  %V 1
  %X The risk of life-threatening COVID-19 pneumonia increases sharply after 65 years of age, but other epidemiological risk factors, genetic or otherwise, are modest. Various rare monogenic inborn errors of type I interferons (IFNs) underlie critical disease, and neutralizing autoantibodies against type I IFNs account for at least 10% of critical cases.
  

• 1.

  Rodriguez, L., and Brodin, P. (2020) Unraveling the Immune Response in Severe COVID-19, Journal of Clinical Immunology 40, 958–959.

  URLBibTeXEndNoteDOIBibSonomy

  @article{Rodriguez2020,
  author = {Rodriguez, Lucie and Brodin, Petter},
  journal = {Journal of Clinical Immunology},
  keywords = {Covid-19},
  month = {oct},
  number = 7,
  pages = {958--959},
  title = {Unraveling the Immune Response in Severe COVID-19},
  volume = 40,
  year = 2020
  }
  

  %0 Journal Article
  %1 Rodriguez2020
  %A Rodriguez, Lucie
  %A Brodin, Petter
  %D 2020
  %J Journal of Clinical Immunology
  %N 7
  %P 958--959
  %R 10.1007/s10875-020-00849-9
  %T Unraveling the Immune Response in Severe COVID-19
  %U https://doi.org/10.1007/s10875-020-00849-9
  %V 40
  

• 1.

  Arias, et al (Ed.). (2020) Auto-antibodies against type I IFNs in patients with life-threatening COVID-19, Science, American Association for the Advancement of Science.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

  @article{Bastardeabd4585,
  abstract = {Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.},
  editor = {Arias, et al},
  journal = {Science},
  keywords = {Covid-19},
  publisher = {American Association for the Advancement of Science},
  title = {Auto-antibodies against type I IFNs in patients with life-threatening COVID-19},
  year = 2020
  }
  

  %0 Journal Article
  %1 Bastardeabd4585
  %D 2020
  %E Arias, et al
  %I American Association for the Advancement of Science
  %J Science
  %R 10.1126/science.abd4585
  %T Auto-antibodies against type I IFNs in patients with life-threatening COVID-19
  %U https://science.sciencemag.org/content/early/2020/09/23/science.abd4585
  %X Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
  

• 1.

  Consiglio, C. R., Cotugno, N., Sardh, F., Pou, C., Amodio, D., Rodriguez, L., Tan, Z., Zicari, S., Ruggiero, A., Pascucci, G. R., Santilli, V., Campbell, T., Bryceson, Y., Eriksson, D., Wang, J., Marchesi, A., Lakshmikanth, T., Campana, A., Villani, A., Rossi, P., Landegren, N., Palma, P., and Brodin, P. (2020) The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19, Cell.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4–6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.

  @article{CONSIGLIO2020,
  abstract = {Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4–6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.},
  author = {Consiglio, Camila Rosat and Cotugno, Nicola and Sardh, Fabian and Pou, Christian and Amodio, Donato and Rodriguez, Lucie and Tan, Ziyang and Zicari, Sonia and Ruggiero, Alessandra and Pascucci, Giuseppe Rubens and Santilli, Veronica and Campbell, Tessa and Bryceson, Yenan and Eriksson, Daniel and Wang, Jun and Marchesi, Alessandra and Lakshmikanth, Tadepally and Campana, Andrea and Villani, Alberto and Rossi, Paolo and Landegren, Nils and Palma, Paolo and Brodin, Petter},
  journal = {Cell},
  keywords = {MIS-C},
  title = {The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19},
  year = 2020
  }
  

  %0 Journal Article
  %1 CONSIGLIO2020
  %A Consiglio, Camila Rosat
  %A Cotugno, Nicola
  %A Sardh, Fabian
  %A Pou, Christian
  %A Amodio, Donato
  %A Rodriguez, Lucie
  %A Tan, Ziyang
  %A Zicari, Sonia
  %A Ruggiero, Alessandra
  %A Pascucci, Giuseppe Rubens
  %A Santilli, Veronica
  %A Campbell, Tessa
  %A Bryceson, Yenan
  %A Eriksson, Daniel
  %A Wang, Jun
  %A Marchesi, Alessandra
  %A Lakshmikanth, Tadepally
  %A Campana, Andrea
  %A Villani, Alberto
  %A Rossi, Paolo
  %A Landegren, Nils
  %A Palma, Paolo
  %A Brodin, Petter
  %D 2020
  %J Cell
  %R https://doi.org/10.1016/j.cell.2020.09.016
  %T The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19
  %U http://www.sciencedirect.com/science/article/pii/S0092867420311570
  %X Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4–6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.
  

• 1.

  Brodin, P. (2019) Systems-level patterns emerge., Nature Reviews Immunology 19, 87–88.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Brodin, Petter},
  journal = {Nature Reviews Immunology},
  keywords = {Systems immunology},
  month = {February},
  number = 2,
  pages = {87-88},
  title = {Systems-level patterns emerge.},
  volume = 19,
  year = 2019
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Brodin, Petter
  %D 2019
  %J Nature Reviews Immunology
  %N 2
  %P 87-88
  %R 10.1038/s41577-018-0106-3
  %T Systems-level patterns emerge.
  %V 19
  

• 1.

  Bekele, Y., Lakshmikanth, T., Chen, Y., Mikes, J., Nasi, A., Petkov, S., Hejdeman, B., Brodin, P., and Chiodi, F. (2019) Mass cytometry identifies distinct CD4+ T cell clusters distinguishing HIV-1-infected patients according to antiretroviral therapy initiation., JCI insight 4.

  AbstractBibTeXEndNoteDOIBibSonomy

  Recent guidelines recommend antiretroviral therapy (ART) to be administered as early as possible during HIV-1 infection. Few studies addressed the immunological benefit of commencing ART during the acute phase of infection. We used mass cytometry to characterize blood CD4+ T cells from HIV-1-infected patients who initiated ART during acute or chronic phase of infection. Using this method, we analyzed a large number of markers on millions of individual immune cells. The results revealed that CD4+ T cell clusters with high expression of CD27, CD28, CD127, and CD44, whose function involves T cell migration to inflamed tissues and survival, are more abundant in healthy controls and patients initiating ART during the acute phase; on the contrary, CD4+ T cell clusters in patients initiating ART during the chronic phase had reduced expression of these markers. The results are suggestive of a better preserved immune function in HIV-1-infected patients initiating ART during acute infection.

  @article{noauthororeditor,
  abstract = {Recent guidelines recommend antiretroviral therapy (ART) to be administered as early as possible during HIV-1 infection. Few studies addressed the immunological benefit of commencing ART during the acute phase of infection. We used mass cytometry to characterize blood CD4+ T cells from HIV-1-infected patients who initiated ART during acute or chronic phase of infection. Using this method, we analyzed a large number of markers on millions of individual immune cells. The results revealed that CD4+ T cell clusters with high expression of CD27, CD28, CD127, and CD44, whose function involves T cell migration to inflamed tissues and survival, are more abundant in healthy controls and patients initiating ART during the acute phase; on the contrary, CD4+ T cell clusters in patients initiating ART during the chronic phase had reduced expression of these markers. The results are suggestive of a better preserved immune function in HIV-1-infected patients initiating ART during acute infection.},
  author = {Bekele, Yonas and Lakshmikanth, Tadepally and Chen, Yang and Mikes, Jaromir and Nasi, Aikaterini and Petkov, Stefan and Hejdeman, Bo and Brodin, Petter and Chiodi, Francesca},
  journal = {JCI insight},
  keywords = {HIV},
  month = {February},
  number = 3,
  title = {Mass cytometry identifies distinct CD4+ T cell clusters distinguishing HIV-1-infected patients according to antiretroviral therapy initiation.},
  volume = 4,
  year = 2019
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Bekele, Yonas
  %A Lakshmikanth, Tadepally
  %A Chen, Yang
  %A Mikes, Jaromir
  %A Nasi, Aikaterini
  %A Petkov, Stefan
  %A Hejdeman, Bo
  %A Brodin, Petter
  %A Chiodi, Francesca
  %D 2019
  %J JCI insight
  %N 3
  %R 10.1172/jci.insight.125442
  %T Mass cytometry identifies distinct CD4+ T cell clusters distinguishing HIV-1-infected patients according to antiretroviral therapy initiation.
  %V 4
  %X Recent guidelines recommend antiretroviral therapy (ART) to be administered as early as possible during HIV-1 infection. Few studies addressed the immunological benefit of commencing ART during the acute phase of infection. We used mass cytometry to characterize blood CD4+ T cells from HIV-1-infected patients who initiated ART during acute or chronic phase of infection. Using this method, we analyzed a large number of markers on millions of individual immune cells. The results revealed that CD4+ T cell clusters with high expression of CD27, CD28, CD127, and CD44, whose function involves T cell migration to inflamed tissues and survival, are more abundant in healthy controls and patients initiating ART during the acute phase; on the contrary, CD4+ T cell clusters in patients initiating ART during the chronic phase had reduced expression of these markers. The results are suggestive of a better preserved immune function in HIV-1-infected patients initiating ART during acute infection.
  

• 1.

  Ramsköld, D., Parodis, I., Lakshmikanth, T., Sippl, N., Khademi, M., Chen, Y., Zickert, A., Mikeš, J., Achour, A., Amara, K., Piehl, F., Brodin, P., Gunnarsson, I., and Malmström, V. (2019) B cell alterations during BAFF inhibition with belimumab in SLE, EBioMedicine 40, 517–527.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which exhibits multiple B cell abnormalities including expanded populations of memory B cells and elevated levels of autoantibodies. Belimumab is a monoclonal antibody targeting the B cell cytokine BAFF (a.k.a. BLyS), approved for the treatment of SLE. Methods In this prospective cohort study, B cells from peripheral blood of 23 SLE patients initiating belimumab treatment and followed longitudinally for up to three years, were assessed using mass cytometry. Findings B cells decreased during the study period, with a rapid decrease of both naïve and CD11c+CD21− B cells at the first follow-up visit, followed by a continuous reduction at subsequent follow-ups. In contrast, plasma cells and switched memory B cells remained stable throughout the study. The observed immunological changes correlated with early, but not late, clinical improvements. Moreover, high baseline B cell counts were predictive of failure to attain low disease activity. In summary, our data unveiled both rapid and gradual later therapy-associated alterations of both known and unforeseen B cell phenotypes. Interpretation Our results suggest that evaluation of B cell counts might prove useful prior to initiation of belimumab treatment and that early treatment evaluation and discontinuation might underestimate delayed clinical improvements resultant of late B cell changes.

  @article{RAMSKOLD2019517,
  abstract = {Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which exhibits multiple B cell abnormalities including expanded populations of memory B cells and elevated levels of autoantibodies. Belimumab is a monoclonal antibody targeting the B cell cytokine BAFF (a.k.a. BLyS), approved for the treatment of SLE. Methods In this prospective cohort study, B cells from peripheral blood of 23 SLE patients initiating belimumab treatment and followed longitudinally for up to three years, were assessed using mass cytometry. Findings B cells decreased during the study period, with a rapid decrease of both naïve and CD11c+CD21− B cells at the first follow-up visit, followed by a continuous reduction at subsequent follow-ups. In contrast, plasma cells and switched memory B cells remained stable throughout the study. The observed immunological changes correlated with early, but not late, clinical improvements. Moreover, high baseline B cell counts were predictive of failure to attain low disease activity. In summary, our data unveiled both rapid and gradual later therapy-associated alterations of both known and unforeseen B cell phenotypes. Interpretation Our results suggest that evaluation of B cell counts might prove useful prior to initiation of belimumab treatment and that early treatment evaluation and discontinuation might underestimate delayed clinical improvements resultant of late B cell changes.},
  author = {Ramsköld, Daniel and Parodis, Ioannis and Lakshmikanth, Tadepally and Sippl, Natalie and Khademi, Mohsen and Chen, Yang and Zickert, Agneta and Mikeš, Jaromír and Achour, Adnane and Amara, Khaled and Piehl, Fredrik and Brodin, Petter and Gunnarsson, Iva and Malmström, Vivianne},
  journal = {EBioMedicine},
  keywords = {B cells},
  pages = {517 - 527},
  title = {B cell alterations during BAFF inhibition with belimumab in SLE},
  volume = 40,
  year = 2019
  }
  

  %0 Journal Article
  %1 RAMSKOLD2019517
  %A Ramsköld, Daniel
  %A Parodis, Ioannis
  %A Lakshmikanth, Tadepally
  %A Sippl, Natalie
  %A Khademi, Mohsen
  %A Chen, Yang
  %A Zickert, Agneta
  %A Mikeš, Jaromír
  %A Achour, Adnane
  %A Amara, Khaled
  %A Piehl, Fredrik
  %A Brodin, Petter
  %A Gunnarsson, Iva
  %A Malmström, Vivianne
  %D 2019
  %J EBioMedicine
  %P 517 - 527
  %R https://doi.org/10.1016/j.ebiom.2018.12.035
  %T B cell alterations during BAFF inhibition with belimumab in SLE
  %U http://www.sciencedirect.com/science/article/pii/S2352396418306121
  %V 40
  %X Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which exhibits multiple B cell abnormalities including expanded populations of memory B cells and elevated levels of autoantibodies. Belimumab is a monoclonal antibody targeting the B cell cytokine BAFF (a.k.a. BLyS), approved for the treatment of SLE. Methods In this prospective cohort study, B cells from peripheral blood of 23 SLE patients initiating belimumab treatment and followed longitudinally for up to three years, were assessed using mass cytometry. Findings B cells decreased during the study period, with a rapid decrease of both naïve and CD11c+CD21− B cells at the first follow-up visit, followed by a continuous reduction at subsequent follow-ups. In contrast, plasma cells and switched memory B cells remained stable throughout the study. The observed immunological changes correlated with early, but not late, clinical improvements. Moreover, high baseline B cell counts were predictive of failure to attain low disease activity. In summary, our data unveiled both rapid and gradual later therapy-associated alterations of both known and unforeseen B cell phenotypes. Interpretation Our results suggest that evaluation of B cell counts might prove useful prior to initiation of belimumab treatment and that early treatment evaluation and discontinuation might underestimate delayed clinical improvements resultant of late B cell changes.
  

• 1.

  Lakshmikanth, T., and Brodin, P. (2019) Systems-Level Immune Monitoring by Mass Cytometry. In Immune Checkpoint Blockade: Methods and Protocols (Pico de Coana, Y., Ed.), pp. 33–48, Springer New York, New York, NY.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  As therapies involving the modulation, stimulation, and deliberate excitation of the immune system are becoming routine, better methods for monitoring immune responses in human patients are needed. Mass cytometry allows for detailed profiling of all immune cell populations and their functional responses using a simple blood sample. When combined with appropriate computational analyses, the resolution for distinguishing desired responses from unproductive or even adverse reactions to immunotherapeutic interventions increases. Here we describe a core experimental and computational framework for global, systems-level immune monitoring by mass cytometry.

  @inbook{Lakshmikanth2019,
  abstract = {As therapies involving the modulation, stimulation, and deliberate excitation of the immune system are becoming routine, better methods for monitoring immune responses in human patients are needed. Mass cytometry allows for detailed profiling of all immune cell populations and their functional responses using a simple blood sample. When combined with appropriate computational analyses, the resolution for distinguishing desired responses from unproductive or even adverse reactions to immunotherapeutic interventions increases. Here we describe a core experimental and computational framework for global, systems-level immune monitoring by mass cytometry.},
  address = {New York, NY},
  author = {Lakshmikanth, Tadepally and Brodin, Petter},
  booktitle = {Immune Checkpoint Blockade: Methods and Protocols},
  chapter = {Systems-Level Immune Monitoring by Mass Cytometry},
  editor = {Pico de Coana, Yago},
  keywords = {cytometry mass},
  pages = {33-48},
  publisher = {Springer New York},
  title = {Systems-Level Immune Monitoring by Mass Cytometry},
  volume = 1913,
  year = 2019
  }
  

  %0 Book Section
  %1 Lakshmikanth2019
  %A Lakshmikanth, Tadepally
  %A Brodin, Petter
  %B Immune Checkpoint Blockade: Methods and Protocols
  %C New York, NY
  %D 2019
  %E Pico de Coana, Yago
  %I Springer New York
  %P 33-48
  %R 10.1007/978-1-4939-8979-9_3
  %T Systems-Level Immune Monitoring by Mass Cytometry
  %U https://doi.org/10.1007/978-1-4939-8979-9_3
  %V 1913
  %X As therapies involving the modulation, stimulation, and deliberate excitation of the immune system are becoming routine, better methods for monitoring immune responses in human patients are needed. Mass cytometry allows for detailed profiling of all immune cell populations and their functional responses using a simple blood sample. When combined with appropriate computational analyses, the resolution for distinguishing desired responses from unproductive or even adverse reactions to immunotherapeutic interventions increases. Here we describe a core experimental and computational framework for global, systems-level immune monitoring by mass cytometry.
  %& Systems-Level Immune Monitoring by Mass Cytometry
  %@ 978-1-4939-8979-9
  

• 1.

  Mikes, J., Olin, A., Lakshmikanth, T., Chen, Y., and Brodin, P. (2019) Automated Cell Processing for Mass Cytometry Experiments. In Mass Cytometry: Methods and Protocols (McGuire, H. M., and Ashhurst, T. M., Eds.), pp. 111–123, Springer New York, New York, NY.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Mass cytometry is a powerful technology for high-dimensional single-cell measurements in millions of individual cells. Antibodies and other detection probes are coupled to elemental tags, each with a unique mass and detectable at single-cell resolution using an ICP-MS type of instrument. Given the sensitivity of the detection system, any free metal ions must be carefully removed through multiple rounds of washing in order to prevent background signal. This results in significant loss of cells. Together with cells lost during acquisition, the final data can represent as little as 10% of the starting material, seriously limiting the amount of information that can be extracted from small samples. Furthermore, complex staining protocols introduce experimental variations that limit comparisons across experiments. Here we present a cell processing and staining procedure for mass cytometry fully automated using a liquid handling robotic system and we present measures taken to optimize all steps of the protocol. These advances are applicable to both manual and automated protocols and provide a six-fold higher cell yield as compared to a standard protocol. With this increased yield and improved reproducibility this protocol now allows us to perform mass cytometry analysis using as little as 100 \($\mu$\)L of whole blood as starting material.

  @inbook{Mikes2019,
  abstract = {Mass cytometry is a powerful technology for high-dimensional single-cell measurements in millions of individual cells. Antibodies and other detection probes are coupled to elemental tags, each with a unique mass and detectable at single-cell resolution using an ICP-MS type of instrument. Given the sensitivity of the detection system, any free metal ions must be carefully removed through multiple rounds of washing in order to prevent background signal. This results in significant loss of cells. Together with cells lost during acquisition, the final data can represent as little as 10% of the starting material, seriously limiting the amount of information that can be extracted from small samples. Furthermore, complex staining protocols introduce experimental variations that limit comparisons across experiments. Here we present a cell processing and staining procedure for mass cytometry fully automated using a liquid handling robotic system and we present measures taken to optimize all steps of the protocol. These advances are applicable to both manual and automated protocols and provide a six-fold higher cell yield as compared to a standard protocol. With this increased yield and improved reproducibility this protocol now allows us to perform mass cytometry analysis using as little as 100 \($\mu$\)L of whole blood as starting material.},
  address = {New York, NY},
  author = {Mikes, Jaromir and Olin, Axel and Lakshmikanth, Tadepally and Chen, Yang and Brodin, Petter},
  booktitle = {Mass Cytometry: Methods and Protocols},
  chapter = {Automated Cell Processing for Mass Cytometry Experiments},
  editor = {McGuire, Helen M. and Ashhurst, Thomas M.},
  keywords = {Cytometry Mass},
  pages = {111-123},
  publisher = {Springer New York},
  title = {Automated Cell Processing for Mass Cytometry Experiments},
  volume = 1989,
  year = 2019
  }
  

  %0 Book Section
  %1 Mikes2019
  %A Mikes, Jaromir
  %A Olin, Axel
  %A Lakshmikanth, Tadepally
  %A Chen, Yang
  %A Brodin, Petter
  %B Mass Cytometry: Methods and Protocols
  %C New York, NY
  %D 2019
  %E McGuire, Helen M.
  %E Ashhurst, Thomas M.
  %I Springer New York
  %P 111-123
  %R 10.1007/978-1-4939-9454-0_8
  %T Automated Cell Processing for Mass Cytometry Experiments
  %U https://doi.org/10.1007/978-1-4939-9454-0_8
  %V 1989
  %X Mass cytometry is a powerful technology for high-dimensional single-cell measurements in millions of individual cells. Antibodies and other detection probes are coupled to elemental tags, each with a unique mass and detectable at single-cell resolution using an ICP-MS type of instrument. Given the sensitivity of the detection system, any free metal ions must be carefully removed through multiple rounds of washing in order to prevent background signal. This results in significant loss of cells. Together with cells lost during acquisition, the final data can represent as little as 10% of the starting material, seriously limiting the amount of information that can be extracted from small samples. Furthermore, complex staining protocols introduce experimental variations that limit comparisons across experiments. Here we present a cell processing and staining procedure for mass cytometry fully automated using a liquid handling robotic system and we present measures taken to optimize all steps of the protocol. These advances are applicable to both manual and automated protocols and provide a six-fold higher cell yield as compared to a standard protocol. With this increased yield and improved reproducibility this protocol now allows us to perform mass cytometry analysis using as little as 100 \($\mu$\)L of whole blood as starting material.
  %& Automated Cell Processing for Mass Cytometry Experiments
  %@ 978-1-4939-9454-0
  

• 1.

  Landegren, N., Rosen, L. B., Freyhult, E., Eriksson, D., Fall, T., Smith, G., Ferre, E. M. N., Brodin, P., Sharon, D., Snyder, M., Lionakis, M., Anderson, mark, and Kämpe, O. (2019) Comment on ’AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies’., ELife 8.

  AbstractBibTeXEndNoteDOIBibSonomy

  The AIRE gene plays a key role in the development of central immune tolerance by promoting thymic presentation of tissue-specific molecules. Patients with AIRE-deficiency develop multiple autoimmune manifestations and display autoantibodies against the affected tissues. In 2016 it was reported that: i) the spectrum of autoantibodies in patients with AIRE-deficiency is much broader than previously appreciated; ii) neutralizing autoantibodies to type I interferons (IFNs) could provide protection against type 1 diabetes in these patients (Meyer et al., 2016). We attempted to replicate these new findings using a similar experimental approach in an independent patient cohort, and found no evidence for either conclusion.

  @article{display:flex).nav-primary__list-ms-flex-align:center;align-items:center;display:-ms-flexbox;display:flex;padding-top:0.nav-primary__itemfloat:left;font-family:"Noto,
  abstract = {The AIRE gene plays a key role in the development of central immune tolerance by promoting thymic presentation of tissue-specific molecules. Patients with AIRE-deficiency develop multiple autoimmune manifestations and display autoantibodies against the affected tissues. In 2016 it was reported that: i) the spectrum of autoantibodies in patients with AIRE-deficiency is much broader than previously appreciated; ii) neutralizing autoantibodies to type I interferons (IFNs) could provide protection against type 1 diabetes in these patients (Meyer et al., 2016). We attempted to replicate these new findings using a similar experimental approach in an independent patient cohort, and found no evidence for either conclusion.},
  author = {Landegren, Nils and Rosen, Lindsey B and Freyhult, Eva and Eriksson, Daniel and Fall, Tove and Smith, Gustav and Ferre, Elise M N and Brodin, Petter and Sharon, Donald and Snyder, Michael and Lionakis, Michail and Anderson, mark and Kämpe, Olle},
  journal = {ELife},
  keywords = {AIRE},
  month = {June},
  title = {Comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'.},
  volume = 8,
  year = 2019
  }
  

  %0 Journal Article
  %1 display:flex).nav-primary__list-ms-flex-align:center;align-items:center;display:-ms-flexbox;display:flex;padding-top:0.nav-primary__itemfloat:left;font-family:"Noto
  %A Landegren, Nils
  %A Rosen, Lindsey B
  %A Freyhult, Eva
  %A Eriksson, Daniel
  %A Fall, Tove
  %A Smith, Gustav
  %A Ferre, Elise M N
  %A Brodin, Petter
  %A Sharon, Donald
  %A Snyder, Michael
  %A Lionakis, Michail
  %A Anderson, mark
  %A Kämpe, Olle
  %D 2019
  %J ELife
  %R 10.7554/eLife.43578
  %T Comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'.
  %V 8
  %X The AIRE gene plays a key role in the development of central immune tolerance by promoting thymic presentation of tissue-specific molecules. Patients with AIRE-deficiency develop multiple autoimmune manifestations and display autoantibodies against the affected tissues. In 2016 it was reported that: i) the spectrum of autoantibodies in patients with AIRE-deficiency is much broader than previously appreciated; ii) neutralizing autoantibodies to type I interferons (IFNs) could provide protection against type 1 diabetes in these patients (Meyer et al., 2016). We attempted to replicate these new findings using a similar experimental approach in an independent patient cohort, and found no evidence for either conclusion.
  

• 1.

  Josyula, V. S., Lakshmikanth, T., Mikes, J., Chen, Y., and Brodin, P. (2019) Systems-level immunomonitoring using self-sampled capillary blood, bioRxiv, Cold Spring Harbor Laboratory.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Comprehensive profiling of the human immune system in patients with cancer, autoimmune disease and during infections are providing valuable information that help us understand disease states and discriminate productive from inefficient immune responses and identify possible targets for immune modulation. Recent technical advances now allow for all immune cell populations and hundreds of plasma proteins to be detected using small volume blood samples. To democratize such systems-immunological analyses, further simplified blood sampling and preservation will be important. Here we describe that blood obtained via a nearly painless self-sampling device of 100 microliter of capillary blood that is preserved and frozen, can simplify systems-level immunomonitoring studies.

  @article{Josyula694521,
  abstract = {Comprehensive profiling of the human immune system in patients with cancer, autoimmune disease and during infections are providing valuable information that help us understand disease states and discriminate productive from inefficient immune responses and identify possible targets for immune modulation. Recent technical advances now allow for all immune cell populations and hundreds of plasma proteins to be detected using small volume blood samples. To democratize such systems-immunological analyses, further simplified blood sampling and preservation will be important. Here we describe that blood obtained via a nearly painless self-sampling device of 100 microliter of capillary blood that is preserved and frozen, can simplify systems-level immunomonitoring studies.},
  author = {Josyula, Vijay Sai and Lakshmikanth, Tadepally and Mikes, Jaromir and Chen, Yang and Brodin, Petter},
  journal = {bioRxiv},
  keywords = {TAP},
  publisher = {Cold Spring Harbor Laboratory},
  title = {Systems-level immunomonitoring using self-sampled capillary blood},
  year = 2019
  }
  

  %0 Journal Article
  %1 Josyula694521
  %A Josyula, Vijay Sai
  %A Lakshmikanth, Tadepally
  %A Mikes, Jaromir
  %A Chen, Yang
  %A Brodin, Petter
  %D 2019
  %I Cold Spring Harbor Laboratory
  %J bioRxiv
  %R 10.1101/694521
  %T Systems-level immunomonitoring using self-sampled capillary blood
  %U https://www.biorxiv.org/content/early/2019/07/08/694521
  %X Comprehensive profiling of the human immune system in patients with cancer, autoimmune disease and during infections are providing valuable information that help us understand disease states and discriminate productive from inefficient immune responses and identify possible targets for immune modulation. Recent technical advances now allow for all immune cell populations and hundreds of plasma proteins to be detected using small volume blood samples. To democratize such systems-immunological analyses, further simplified blood sampling and preservation will be important. Here we describe that blood obtained via a nearly painless self-sampling device of 100 microliter of capillary blood that is preserved and frozen, can simplify systems-level immunomonitoring studies.
  

• 1.

  Tang, Q., Ramsköld, D., Krystufkova, O., Mann, H. F., Wick, C., Dastmalchi, M., Lakshmikanth, T., Chen, Y., Mikes, J., Alexanderson, H., Achour, A., Brodin, P., Lundberg, I. E., and Malmström, V. (2019) Effect of CTLA4-Ig (abatacept) treatment on T cells and B cells in peripheral blood of patients with polymyositis and dermatomyositis., Scandinavian journal of immunology 89.

  AbstractBibTeXEndNoteDOIBibSonomy

  We aimed to evaluate in vivo effects of abatacept on phenotypes of T and B cells in the circulation of myositis patients in a sub‐study of the ARTEMIS trial. Twelve patients with paired frozen PBMCs before and after 6‐month abatacept treatment were included in this sub‐study where mass cytometry (CyTOF) was chosen as a technology to be tested for its utility in a real‐life clinical immune monitoring setting. Using CyTOF, the peripheral T cell phenotypes demonstrated considerable variation over time and between individuals precluding the identification of treatment‐specific changes. We therefore conclude that studies of patient cohorts displaying wide clinical heterogeneity using mass cytometry must be relatively large in order to be suited for discovery research and immune monitoring. Still, we did find some correlations with functional muscle outcome, namely positive correlations between the ratio of CD4+ T cells and CD8+ T cells (CD4/CD8) in peripheral blood samples both at baseline and after treatment with muscle endurance improvement as assessed by the functional index‐2 (FI‐2) test. Our data suggest that the CD4/CD8 ratio in circulation at time of active disease may be a predictor of treatment efficacy in myositis patients.

  @article{noauthororeditor,
  abstract = {We aimed to evaluate in vivo effects of abatacept on phenotypes of T and B cells in the circulation of myositis patients in a sub‐study of the ARTEMIS trial. Twelve patients with paired frozen PBMCs before and after 6‐month abatacept treatment were included in this sub‐study where mass cytometry (CyTOF) was chosen as a technology to be tested for its utility in a real‐life clinical immune monitoring setting. Using CyTOF, the peripheral T cell phenotypes demonstrated considerable variation over time and between individuals precluding the identification of treatment‐specific changes. We therefore conclude that studies of patient cohorts displaying wide clinical heterogeneity using mass cytometry must be relatively large in order to be suited for discovery research and immune monitoring. Still, we did find some correlations with functional muscle outcome, namely positive correlations between the ratio of CD4+ T cells and CD8+ T cells (CD4/CD8) in peripheral blood samples both at baseline and after treatment with muscle endurance improvement as assessed by the functional index‐2 (FI‐2) test. Our data suggest that the CD4/CD8 ratio in circulation at time of active disease may be a predictor of treatment efficacy in myositis patients.},
  author = {Tang, Quan and Ramsköld, Daniel and Krystufkova, Olga and Mann, Herman F and Wick, Cecilia and Dastmalchi, Maryam and Lakshmikanth, Tadepally and Chen, Yang and Mikes, Jaromir and Alexanderson, Helene and Achour, Adnane and Brodin, Petter and Lundberg, Ingrid E and Malmström, Vivianne},
  journal = {Scandinavian journal of immunology},
  keywords = {dermatomyositis polymyositis,},
  month = {January},
  number = 1,
  title = {Effect of CTLA4-Ig (abatacept) treatment on T cells and B cells in peripheral blood of patients with polymyositis and dermatomyositis.},
  volume = 89,
  year = 2019
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Tang, Quan
  %A Ramsköld, Daniel
  %A Krystufkova, Olga
  %A Mann, Herman F
  %A Wick, Cecilia
  %A Dastmalchi, Maryam
  %A Lakshmikanth, Tadepally
  %A Chen, Yang
  %A Mikes, Jaromir
  %A Alexanderson, Helene
  %A Achour, Adnane
  %A Brodin, Petter
  %A Lundberg, Ingrid E
  %A Malmström, Vivianne
  %D 2019
  %J Scandinavian journal of immunology
  %N 1
  %R https://doi-org.proxy.kib.ki.se/10.1111/sji.12732
  %T Effect of CTLA4-Ig (abatacept) treatment on T cells and B cells in peripheral blood of patients with polymyositis and dermatomyositis.
  %V 89
  %X We aimed to evaluate in vivo effects of abatacept on phenotypes of T and B cells in the circulation of myositis patients in a sub‐study of the ARTEMIS trial. Twelve patients with paired frozen PBMCs before and after 6‐month abatacept treatment were included in this sub‐study where mass cytometry (CyTOF) was chosen as a technology to be tested for its utility in a real‐life clinical immune monitoring setting. Using CyTOF, the peripheral T cell phenotypes demonstrated considerable variation over time and between individuals precluding the identification of treatment‐specific changes. We therefore conclude that studies of patient cohorts displaying wide clinical heterogeneity using mass cytometry must be relatively large in order to be suited for discovery research and immune monitoring. Still, we did find some correlations with functional muscle outcome, namely positive correlations between the ratio of CD4+ T cells and CD8+ T cells (CD4/CD8) in peripheral blood samples both at baseline and after treatment with muscle endurance improvement as assessed by the functional index‐2 (FI‐2) test. Our data suggest that the CD4/CD8 ratio in circulation at time of active disease may be a predictor of treatment efficacy in myositis patients.
  

• 1.

  Sundling, C., Rönnberg, C., Yman, V., Asghar, M., Jahnmatz, P., Lakshmikanth, T., Chen, Y., Mikes, J., Forsell, M. N., Sondén, K., Achour, A., Brodin, P., Persson, K. E., and Färnert, A. (2019) B cell profiling in malaria reveals expansion and remodelling of CD11c+ B cell subsets, JCI Insight 5.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Humoral immunity is important in limiting clinical disease in malaria, yet the longitudinal B cell response to infection remains unclear. We performed a 1-year prospective study in patients treated for acute P. falciparum malaria for the first time, or with previous exposure to the disease. Using an unbiased exploratory approach with mass cytometry, followed by targeted flow cytometry, we found that ~80% of mature B cells that proliferated in response to acute infection expressed CD11c. Only ~40% of CD11c+ B cells displayed an atypical B cell phenotype, with the remaining cells primarily made up of activated- and resting memory B cells. The CD11c+ B cells expanded rapidly following infection, with previous exposure to malaria resulting in a significantly larger increase compared to individuals with primary infection. This was attributed to an expansion of switched CD11c+ B cells that was absent in primary infected individuals. The rate of contraction of the CD11c+ B cell compartment was independent of previous exposure to malaria and displayed a slow decay with a half-life of ~300 days. Collectively, these results identify CD11c as a marker of B cells responding to malaria and further highlight differences in primary- and secondary B cell responses during infection.

  @article{Sundling:2019:JCI-Insight:30939125,
  abstract = {Humoral immunity is important in limiting clinical disease in malaria, yet the longitudinal B cell response to infection remains unclear. We performed a 1-year prospective study in patients treated for acute P. falciparum malaria for the first time, or with previous exposure to the disease. Using an unbiased exploratory approach with mass cytometry, followed by targeted flow cytometry, we found that ~80% of mature B cells that proliferated in response to acute infection expressed CD11c. Only ~40% of CD11c+ B cells displayed an atypical B cell phenotype, with the remaining cells primarily made up of activated- and resting memory B cells. The CD11c+ B cells expanded rapidly following infection, with previous exposure to malaria resulting in a significantly larger increase compared to individuals with primary infection. This was attributed to an expansion of switched CD11c+ B cells that was absent in primary infected individuals. The rate of contraction of the CD11c+ B cell compartment was independent of previous exposure to malaria and displayed a slow decay with a half-life of ~300 days. Collectively, these results identify CD11c as a marker of B cells responding to malaria and further highlight differences in primary- and secondary B cell responses during infection.},
  author = {Sundling, C and Rönnberg, C and Yman, V and Asghar, M and Jahnmatz, P and Lakshmikanth, T and Chen, Y and Mikes, J and Forsell, M N and Sondén, K and Achour, A and Brodin, P and Persson, K E and Färnert, A},
  journal = {JCI Insight},
  keywords = {B cells},
  month = {apr},
  title = {B cell profiling in malaria reveals expansion and remodelling of CD11c+ B cell subsets},
  volume = 5,
  year = 2019
  }
  

  %0 Journal Article
  %1 Sundling:2019:JCI-Insight:30939125
  %A Sundling, C
  %A Rönnberg, C
  %A Yman, V
  %A Asghar, M
  %A Jahnmatz, P
  %A Lakshmikanth, T
  %A Chen, Y
  %A Mikes, J
  %A Forsell, M N
  %A Sondén, K
  %A Achour, A
  %A Brodin, P
  %A Persson, K E
  %A Färnert, A
  %D 2019
  %J JCI Insight
  %R 10.1172/jci.insight.126492
  %T B cell profiling in malaria reveals expansion and remodelling of CD11c+ B cell subsets
  %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538354/
  %V 5
  %X Humoral immunity is important in limiting clinical disease in malaria, yet the longitudinal B cell response to infection remains unclear. We performed a 1-year prospective study in patients treated for acute P. falciparum malaria for the first time, or with previous exposure to the disease. Using an unbiased exploratory approach with mass cytometry, followed by targeted flow cytometry, we found that ~80% of mature B cells that proliferated in response to acute infection expressed CD11c. Only ~40% of CD11c+ B cells displayed an atypical B cell phenotype, with the remaining cells primarily made up of activated- and resting memory B cells. The CD11c+ B cells expanded rapidly following infection, with previous exposure to malaria resulting in a significantly larger increase compared to individuals with primary infection. This was attributed to an expansion of switched CD11c+ B cells that was absent in primary infected individuals. The rate of contraction of the CD11c+ B cell compartment was independent of previous exposure to malaria and displayed a slow decay with a half-life of ~300 days. Collectively, these results identify CD11c as a marker of B cells responding to malaria and further highlight differences in primary- and secondary B cell responses during infection.
  

• 1.

  Achten, N. B., Klingenberg, C., Benitz, W. E., Stocker, M., Schlapbach, L. J., Giannoni, E., Bokelaar, R., Driessen, G. J. A., Brodin, P., Uthaya, S., van Rossum, A. M. C., and Plötz, F. B. (2019) Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic Review and Meta-analysis., JAMA pediatrics.

  AbstractBibTeXEndNoteDOIBibSonomy

  IMPORTANCE: The neonatal early-onset sepsis (EOS) calculator is a clinical risk stratification tool increasingly used to guide the use of empirical antibiotics for newborns. Evidence on the effectiveness and safety of the EOS calculator is essential to inform clinicians considering implementation. OBJECTIVE: To assess the association between management of neonatal EOS guided by the neonatal EOS calculator (compared with conventional management strategies) and reduction in antibiotic therapy for newborns. DATA SOURCES: Electronic searches in MEDLINE, Embase, Web of Science, and Google Scholar were conducted from 2011 (introduction of the EOS calculator model) through January 31, 2019. STUDY SELECTION: All studies with original data that compared management guided by the EOS calculator with conventional management strategies for allocating antibiotic therapy to newborns suspected to have EOS were included. DATA EXTRACTION AND SYNTHESIS: Following PRISMA-P guidelines, relevant data were extracted from full-text articles and supplements. CHARMS (Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) tools were used to assess the risk of bias and quality of evidence. Meta-analysis using a random-effects model was conducted for studies with separate cohorts for EOS calculator and conventional management strategies. MAIN OUTCOMES AND MEASURES: The difference in percentage of newborns treated with empirical antibiotics for suspected or proven EOS between management guided by the EOS calculator and conventional management strategies. Safety-related outcomes involved missed cases of EOS, readmissions, treatment delay, morbidity, and mortality. RESULTS: Thirteen relevant studies analyzing a total of 175 752 newborns were included. All studies found a substantially lower relative risk (range, 3%-60%) for empirical antibiotic therapy, favoring the EOS calculator. Meta-analysis revealed a relative risk of antibiotic use of 56% (95% CI, 53%-59%) in before-after studies including newborns regardless of exposure to chorioamnionitis. Evidence on safety was limited, but proportions of missed cases of EOS were comparable between management guided by the EOS calculator (5 of 18 [28%]) and conventional management strategies (8 of 28 [29%]) (pooled odds ratio, 0.96; 95% CI, 0.26-3.52; P = .95). CONCLUSIONS AND RELEVANCE: Use of the neonatal EOS calculator is associated with a substantial reduction in the use of empirical antibiotics for suspected EOS. Available evidence regarding safety of the use of the EOS calculator is limited, but shows no indication of inferiority compared with conventional management strategies.

  @article{noauthororeditor,
  abstract = {IMPORTANCE: The neonatal early-onset sepsis (EOS) calculator is a clinical risk stratification tool increasingly used to guide the use of empirical antibiotics for newborns. Evidence on the effectiveness and safety of the EOS calculator is essential to inform clinicians considering implementation. OBJECTIVE: To assess the association between management of neonatal EOS guided by the neonatal EOS calculator (compared with conventional management strategies) and reduction in antibiotic therapy for newborns. DATA SOURCES: Electronic searches in MEDLINE, Embase, Web of Science, and Google Scholar were conducted from 2011 (introduction of the EOS calculator model) through January 31, 2019. STUDY SELECTION: All studies with original data that compared management guided by the EOS calculator with conventional management strategies for allocating antibiotic therapy to newborns suspected to have EOS were included. DATA EXTRACTION AND SYNTHESIS: Following PRISMA-P guidelines, relevant data were extracted from full-text articles and supplements. CHARMS (Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) tools were used to assess the risk of bias and quality of evidence. Meta-analysis using a random-effects model was conducted for studies with separate cohorts for EOS calculator and conventional management strategies. MAIN OUTCOMES AND MEASURES: The difference in percentage of newborns treated with empirical antibiotics for suspected or proven EOS between management guided by the EOS calculator and conventional management strategies. Safety-related outcomes involved missed cases of EOS, readmissions, treatment delay, morbidity, and mortality. RESULTS: Thirteen relevant studies analyzing a total of 175 752 newborns were included. All studies found a substantially lower relative risk (range, 3%-60%) for empirical antibiotic therapy, favoring the EOS calculator. Meta-analysis revealed a relative risk of antibiotic use of 56% (95% CI, 53%-59%) in before-after studies including newborns regardless of exposure to chorioamnionitis. Evidence on safety was limited, but proportions of missed cases of EOS were comparable between management guided by the EOS calculator (5 of 18 [28%]) and conventional management strategies (8 of 28 [29%]) (pooled odds ratio, 0.96; 95% CI, 0.26-3.52; P = .95). CONCLUSIONS AND RELEVANCE: Use of the neonatal EOS calculator is associated with a substantial reduction in the use of empirical antibiotics for suspected EOS. Available evidence regarding safety of the use of the EOS calculator is limited, but shows no indication of inferiority compared with conventional management strategies.},
  author = {Achten, Niek B and Klingenberg, Claus and Benitz, William E and Stocker, Martin and Schlapbach, Luregn J and Giannoni, Eric and Bokelaar, Robin and Driessen, Gertjan J A and Brodin, Petter and Uthaya, Sabita and van Rossum, Annemarie M C and Plötz, Frans B},
  journal = {JAMA pediatrics},
  keywords = {Antibiotics Neonatal,},
  title = {Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic Review and Meta-analysis.},
  year = 2019
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Achten, Niek B
  %A Klingenberg, Claus
  %A Benitz, William E
  %A Stocker, Martin
  %A Schlapbach, Luregn J
  %A Giannoni, Eric
  %A Bokelaar, Robin
  %A Driessen, Gertjan J A
  %A Brodin, Petter
  %A Uthaya, Sabita
  %A van Rossum, Annemarie M C
  %A Plötz, Frans B
  %D 2019
  %J JAMA pediatrics
  %R 10.1001/jamapediatrics.2019.2825
  %T Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic Review and Meta-analysis.
  %X IMPORTANCE: The neonatal early-onset sepsis (EOS) calculator is a clinical risk stratification tool increasingly used to guide the use of empirical antibiotics for newborns. Evidence on the effectiveness and safety of the EOS calculator is essential to inform clinicians considering implementation. OBJECTIVE: To assess the association between management of neonatal EOS guided by the neonatal EOS calculator (compared with conventional management strategies) and reduction in antibiotic therapy for newborns. DATA SOURCES: Electronic searches in MEDLINE, Embase, Web of Science, and Google Scholar were conducted from 2011 (introduction of the EOS calculator model) through January 31, 2019. STUDY SELECTION: All studies with original data that compared management guided by the EOS calculator with conventional management strategies for allocating antibiotic therapy to newborns suspected to have EOS were included. DATA EXTRACTION AND SYNTHESIS: Following PRISMA-P guidelines, relevant data were extracted from full-text articles and supplements. CHARMS (Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) tools were used to assess the risk of bias and quality of evidence. Meta-analysis using a random-effects model was conducted for studies with separate cohorts for EOS calculator and conventional management strategies. MAIN OUTCOMES AND MEASURES: The difference in percentage of newborns treated with empirical antibiotics for suspected or proven EOS between management guided by the EOS calculator and conventional management strategies. Safety-related outcomes involved missed cases of EOS, readmissions, treatment delay, morbidity, and mortality. RESULTS: Thirteen relevant studies analyzing a total of 175 752 newborns were included. All studies found a substantially lower relative risk (range, 3%-60%) for empirical antibiotic therapy, favoring the EOS calculator. Meta-analysis revealed a relative risk of antibiotic use of 56% (95% CI, 53%-59%) in before-after studies including newborns regardless of exposure to chorioamnionitis. Evidence on safety was limited, but proportions of missed cases of EOS were comparable between management guided by the EOS calculator (5 of 18 [28%]) and conventional management strategies (8 of 28 [29%]) (pooled odds ratio, 0.96; 95% CI, 0.26-3.52; P = .95). CONCLUSIONS AND RELEVANCE: Use of the neonatal EOS calculator is associated with a substantial reduction in the use of empirical antibiotics for suspected EOS. Available evidence regarding safety of the use of the EOS calculator is limited, but shows no indication of inferiority compared with conventional management strategies.
  

• 1.

  Brodin, P., Duffy, D., and Quintana-Murci, L. (2019) A Call for Blood—In Human Immunology, Immunity 50, 1335–1336.

  URLBibTeXEndNoteDOIBibSonomy

  @article{BRODIN20191335,
  author = {Brodin, Petter and Duffy, Darragh and Quintana-Murci, Lluis},
  journal = {Immunity},
  keywords = {blood},
  month = {June},
  number = 6,
  pages = {1335 - 1336},
  title = {A Call for Blood—In Human Immunology},
  volume = 50,
  year = 2019
  }
  

  %0 Journal Article
  %1 BRODIN20191335
  %A Brodin, Petter
  %A Duffy, Darragh
  %A Quintana-Murci, Lluis
  %D 2019
  %J Immunity
  %N 6
  %P 1335 - 1336
  %R https://doi.org/10.1016/j.immuni.2019.05.012
  %T A Call for Blood—In Human Immunology
  %U http://www.sciencedirect.com/science/article/pii/S1074761319302328
  %V 50
  

• 1.

  Mold, J. E., Réu, P., Olin, A., Bernard, S., Michaëlsson, J., Rane, S., Yates, A., Khosravi, A., Salehpour, M., Possnert, G., Brodin, P., and Frisén, J. (2019) Cell generation dynamics underlying naive T-cell homeostasis in adult humans, PLOS Biology, Public Library of Science 17, 1–26.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Our pool of naive T cells is critical for protection against new infections and cancers. By measuring remnant 14C from 1960s nuclear bomb blasts that has been incorporated into cellular DNA, this study defines the average age of the naive T-cell pool in healthy adults, revealing the slow, regulated turnover of the naive T-cell pool, supporting its maintenance for a human lifetime.

  @article{10.1371/journal.pbio.3000383,
  abstract = {Our pool of naive T cells is critical for protection against new infections and cancers. By measuring remnant 14C from 1960s nuclear bomb blasts that has been incorporated into cellular DNA, this study defines the average age of the naive T-cell pool in healthy adults, revealing the slow, regulated turnover of the naive T-cell pool, supporting its maintenance for a human lifetime.},
  author = {Mold, Jeff E. and Réu, Pedro and Olin, Axel and Bernard, Samuel and Michaëlsson, Jakob and Rane, Sanket and Yates, Andrew and Khosravi, Azadeh and Salehpour, Mehran and Possnert, Göran and Brodin, Petter and Frisén, Jonas},
  journal = {PLOS Biology},
  keywords = {T cells},
  month = 10,
  number = 10,
  pages = {1-26},
  publisher = {Public Library of Science},
  title = {Cell generation dynamics underlying naive T-cell homeostasis in adult humans},
  volume = 17,
  year = 2019
  }
  

  %0 Journal Article
  %1 10.1371/journal.pbio.3000383
  %A Mold, Jeff E.
  %A Réu, Pedro
  %A Olin, Axel
  %A Bernard, Samuel
  %A Michaëlsson, Jakob
  %A Rane, Sanket
  %A Yates, Andrew
  %A Khosravi, Azadeh
  %A Salehpour, Mehran
  %A Possnert, Göran
  %A Brodin, Petter
  %A Frisén, Jonas
  %D 2019
  %I Public Library of Science
  %J PLOS Biology
  %N 10
  %P 1-26
  %R 10.1371/journal.pbio.3000383
  %T Cell generation dynamics underlying naive T-cell homeostasis in adult humans
  %U https://doi.org/10.1371/journal.pbio.3000383
  %V 17
  %X Our pool of naive T cells is critical for protection against new infections and cancers. By measuring remnant 14C from 1960s nuclear bomb blasts that has been incorporated into cellular DNA, this study defines the average age of the naive T-cell pool in healthy adults, revealing the slow, regulated turnover of the naive T-cell pool, supporting its maintenance for a human lifetime.
  

• 1.

  Lundgren, P., Klevebro, S., Brodin, P., Smith, L. E., Hallberg, B., and Hellström, A. (2019) Leucocytosis is associated with retinopathy of prematurity in extremely preterm infants., Acta pædiatrica 108, 1357–1358.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Lundgren, Pia and Klevebro, Susanna and Brodin, Petter and Smith, Lois E.H and Hallberg, Boubou and Hellström, Ann},
  journal = {Acta pædiatrica},
  keywords = {Preterm},
  month = {March},
  number = 7,
  pages = {1357-1358},
  title = {Leucocytosis is associated with retinopathy of prematurity in extremely preterm infants.},
  volume = 108,
  year = 2019
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Lundgren, Pia
  %A Klevebro, Susanna
  %A Brodin, Petter
  %A Smith, Lois E.H
  %A Hallberg, Boubou
  %A Hellström, Ann
  %D 2019
  %J Acta pædiatrica
  %N 7
  %P 1357-1358
  %R https://doi-org.proxy.kib.ki.se/10.1111/apa.14798
  %T Leucocytosis is associated with retinopathy of prematurity in extremely preterm infants.
  %V 108
  

• 1.

  Brodin, P. (2019) Seeking the ultimate challenge, Nature medicine 25, 1026.

  AbstractBibTeXEndNoteDOIBibSonomy

  Petter Brodin is a pediatrician at the Karolinska University Hospital and an immunologist at Science for Life Laboratory. His lab combines state-of-the-art experimental methods and computational tools to monitor human immune systems in the most comprehensive way possible.

  @article{noauthororeditor,
  abstract = {Petter Brodin is a pediatrician at the Karolinska University Hospital and an immunologist at Science for Life Laboratory. His lab combines state-of-the-art experimental methods and computational tools to monitor human immune systems in the most comprehensive way possible.},
  author = {Brodin, Petter},
  journal = {Nature medicine},
  keywords = {Challenge},
  month = {July},
  number = 7,
  pages = 1026,
  title = {Seeking the ultimate challenge},
  volume = 25,
  year = 2019
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Brodin, Petter
  %D 2019
  %J Nature medicine
  %N 7
  %P 1026
  %R 0.1038/s41591-019-0497-0
  %T Seeking the ultimate challenge
  %V 25
  %X Petter Brodin is a pediatrician at the Karolinska University Hospital and an immunologist at Science for Life Laboratory. His lab combines state-of-the-art experimental methods and computational tools to monitor human immune systems in the most comprehensive way possible.
  

• 1.

  Pou, C., Nkulikiyimfura, D., Henckel, E., Olin, A., Lakshmikanth, T., Mikes, J., Wang, J., Chen, Y., Bernhardsson, A. K., Gustafsson, A., Bohlin, K., and Brodin, P. (2019) The repertoire of maternal anti-viral antibodies in human newborns., Nature medicine 25, 591–596.

  AbstractBibTeXEndNoteDOIBibSonomy

  All circulating immunoglobulin G (IgG) antibodies in human newborns are of maternal origin1 and transferred across the placenta to provide passive immunity until newborn IgG production takes over 15 weeks after birth2. However, maternal IgG can also negatively interfere with newborn vaccine responses3. The concentration of IgG increases sharply during the third trimester of gestation and children delivered extremely preterm are believed to largely lack this passive immunity1,2,4. Antibodies to individual viruses have been reported5-12, but the global repertoire of maternal IgG, its variation in children, and the epitopes targeted are poorly understood. Here, we assess antibodies against 93,904 epitopes from 206 viruses in 32 preterm and 46 term mother-child dyads. We find that extremely preterm children receive comparable repertoires of IgG as term children, albeit at lower absolute concentrations and consequent shorter half-life. Neutralization of the clinically important respiratory syncytial virus (RS-virus) was also comparable until three months of age. These findings have implications for understanding infectious disease susceptibility, vaccine development, and vaccine scheduling in newborn children.

  @article{noauthororeditor,
  abstract = {All circulating immunoglobulin G (IgG) antibodies in human newborns are of maternal origin1 and transferred across the placenta to provide passive immunity until newborn IgG production takes over 15 weeks after birth2. However, maternal IgG can also negatively interfere with newborn vaccine responses3. The concentration of IgG increases sharply during the third trimester of gestation and children delivered extremely preterm are believed to largely lack this passive immunity1,2,4. Antibodies to individual viruses have been reported5-12, but the global repertoire of maternal IgG, its variation in children, and the epitopes targeted are poorly understood. Here, we assess antibodies against 93,904 epitopes from 206 viruses in 32 preterm and 46 term mother-child dyads. We find that extremely preterm children receive comparable repertoires of IgG as term children, albeit at lower absolute concentrations and consequent shorter half-life. Neutralization of the clinically important respiratory syncytial virus (RS-virus) was also comparable until three months of age. These findings have implications for understanding infectious disease susceptibility, vaccine development, and vaccine scheduling in newborn children.},
  author = {Pou, Christian and Nkulikiyimfura, Dieudonné and Henckel, Ewa and Olin, Axel and Lakshmikanth, Tadepally and Mikes, Jaromir and Wang, Jun and Chen, Yang and Bernhardsson, Anna Karin and Gustafsson, Anna and Bohlin, Kajsa and Brodin, Petter},
  journal = {Nature medicine},
  keywords = {Maternal VirScan, antibodies},
  month = {April},
  number = 4,
  pages = {591-596},
  title = {The repertoire of maternal anti-viral antibodies in human newborns.},
  volume = 25,
  year = 2019
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Pou, Christian
  %A Nkulikiyimfura, Dieudonné
  %A Henckel, Ewa
  %A Olin, Axel
  %A Lakshmikanth, Tadepally
  %A Mikes, Jaromir
  %A Wang, Jun
  %A Chen, Yang
  %A Bernhardsson, Anna Karin
  %A Gustafsson, Anna
  %A Bohlin, Kajsa
  %A Brodin, Petter
  %D 2019
  %J Nature medicine
  %N 4
  %P 591-596
  %R 10.1038/s41591-019-0392-8
  %T The repertoire of maternal anti-viral antibodies in human newborns.
  %V 25
  %X All circulating immunoglobulin G (IgG) antibodies in human newborns are of maternal origin1 and transferred across the placenta to provide passive immunity until newborn IgG production takes over 15 weeks after birth2. However, maternal IgG can also negatively interfere with newborn vaccine responses3. The concentration of IgG increases sharply during the third trimester of gestation and children delivered extremely preterm are believed to largely lack this passive immunity1,2,4. Antibodies to individual viruses have been reported5-12, but the global repertoire of maternal IgG, its variation in children, and the epitopes targeted are poorly understood. Here, we assess antibodies against 93,904 epitopes from 206 viruses in 32 preterm and 46 term mother-child dyads. We find that extremely preterm children receive comparable repertoires of IgG as term children, albeit at lower absolute concentrations and consequent shorter half-life. Neutralization of the clinically important respiratory syncytial virus (RS-virus) was also comparable until three months of age. These findings have implications for understanding infectious disease susceptibility, vaccine development, and vaccine scheduling in newborn children.
  

• 1.

  Brodin, P. (2019) The biology of the cell - insights from mass cytometry., FEBS journal 286, 1514–1522.

  AbstractBibTeXEndNoteDOIBibSonomy

  In single-cell biology there is an ongoing push toward more and more comprehensive measurements made in individual cells. By combining measurements of proteins, mRNA, genetic, and epigenetic traits, in contexts of cell stimulation or drug treatment, novel single-cell analyses will help understand the determinants of cellular identity, differentiation decisions, and regulatory mechanisms governing cellular function in health and disease. Mass cytometry is a flexible methodology not only developed toward this aim, allowing analyses of cells in suspension such as blood but also extended for the analyses of tissue sections. Here, I will discuss the different measurements possible by mass cytometry and not only discuss its potential but also its limitations now and in the years to come.

  @article{noauthororeditor,
  abstract = {In single-cell biology there is an ongoing push toward more and more comprehensive measurements made in individual cells. By combining measurements of proteins, mRNA, genetic, and epigenetic traits, in contexts of cell stimulation or drug treatment, novel single-cell analyses will help understand the determinants of cellular identity, differentiation decisions, and regulatory mechanisms governing cellular function in health and disease. Mass cytometry is a flexible methodology not only developed toward this aim, allowing analyses of cells in suspension such as blood but also extended for the analyses of tissue sections. Here, I will discuss the different measurements possible by mass cytometry and not only discuss its potential but also its limitations now and in the years to come.},
  author = {Brodin, Petter},
  journal = {FEBS journal},
  keywords = {Cytometry Mass},
  month = {April},
  number = 8,
  pages = {1514-1522},
  title = {The biology of the cell - insights from mass cytometry.},
  volume = 286,
  year = 2019
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Brodin, Petter
  %D 2019
  %J FEBS journal
  %N 8
  %P 1514-1522
  %R 10.1111/febs.14693
  %T The biology of the cell - insights from mass cytometry.
  %V 286
  %X In single-cell biology there is an ongoing push toward more and more comprehensive measurements made in individual cells. By combining measurements of proteins, mRNA, genetic, and epigenetic traits, in contexts of cell stimulation or drug treatment, novel single-cell analyses will help understand the determinants of cellular identity, differentiation decisions, and regulatory mechanisms governing cellular function in health and disease. Mass cytometry is a flexible methodology not only developed toward this aim, allowing analyses of cells in suspension such as blood but also extended for the analyses of tissue sections. Here, I will discuss the different measurements possible by mass cytometry and not only discuss its potential but also its limitations now and in the years to come.
  

• 1.

  Uhlen, M., Karlsson, M. J., Zhong, W., Tebani, A., Pou, C., Mikes, J., Lakshmikanth, T., Forsström, B., Edfors, F., Odeberg, J., Mardinoglu, A., Zhang, C., von Feilitzen, K., Mulder, J., Sjöstedt, E., Hober, A., Oksvold, P., Zwahlen, M., Ponten, F., Lindskog, C., Sivertsson, Åsa, Fagerberg, L., and Brodin, P. (2019) A genome-wide transcriptomic analysis of protein-coding genes in human blood cells., Science 366.

  AbstractBibTeXEndNoteDOIBibSonomy

  Blood is the predominant source for molecular analyses in humans, both in clinical and research settings. It is the target for many therapeutic strategies, emphasizing the need for comprehensive molecular maps of the cells constituting human blood. In this study, we performed a genome-wide transcriptomic analysis of protein-coding genes in sorted blood immune cell populations to characterize the expression levels of each individual gene across the blood cell types. All data are presented in an interactive, open-access Blood Atlas as part of the Human Protein Atlas and are integrated with expression profiles across all major tissues to provide spatial classification of all protein-coding genes. This allows for a genome-wide exploration of the expression profiles across human immune cell populations and all major human tissues and organs.

  @article{noauthororeditor,
  abstract = {Blood is the predominant source for molecular analyses in humans, both in clinical and research settings. It is the target for many therapeutic strategies, emphasizing the need for comprehensive molecular maps of the cells constituting human blood. In this study, we performed a genome-wide transcriptomic analysis of protein-coding genes in sorted blood immune cell populations to characterize the expression levels of each individual gene across the blood cell types. All data are presented in an interactive, open-access Blood Atlas as part of the Human Protein Atlas and are integrated with expression profiles across all major tissues to provide spatial classification of all protein-coding genes. This allows for a genome-wide exploration of the expression profiles across human immune cell populations and all major human tissues and organs.},
  author = {Uhlen, Mathias and Karlsson, Max J and Zhong, Wen and Tebani, Abdellah and Pou, Christian and Mikes, Jaromir and Lakshmikanth, Tadepally and Forsström, Björn and Edfors, Fredrik and Odeberg, Jacob and Mardinoglu, Adil and Zhang, Cheng and von Feilitzen, Kalle and Mulder, Jan and Sjöstedt, Evelina and Hober, Andreas and Oksvold, Per and Zwahlen, Martin and Ponten, Fredrik and Lindskog, Cecilia and Sivertsson, Åsa and Fagerberg, Linn and Brodin, Petter},
  journal = {Science},
  keywords = {Atlas Protein},
  number = 6472,
  title = {A genome-wide transcriptomic analysis of protein-coding genes in human blood cells.},
  volume = 366,
  year = 2019
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Uhlen, Mathias
  %A Karlsson, Max J
  %A Zhong, Wen
  %A Tebani, Abdellah
  %A Pou, Christian
  %A Mikes, Jaromir
  %A Lakshmikanth, Tadepally
  %A Forsström, Björn
  %A Edfors, Fredrik
  %A Odeberg, Jacob
  %A Mardinoglu, Adil
  %A Zhang, Cheng
  %A von Feilitzen, Kalle
  %A Mulder, Jan
  %A Sjöstedt, Evelina
  %A Hober, Andreas
  %A Oksvold, Per
  %A Zwahlen, Martin
  %A Ponten, Fredrik
  %A Lindskog, Cecilia
  %A Sivertsson, Åsa
  %A Fagerberg, Linn
  %A Brodin, Petter
  %D 2019
  %J Science
  %N 6472
  %R 10.1126/science.aax9198
  %T A genome-wide transcriptomic analysis of protein-coding genes in human blood cells.
  %V 366
  %X Blood is the predominant source for molecular analyses in humans, both in clinical and research settings. It is the target for many therapeutic strategies, emphasizing the need for comprehensive molecular maps of the cells constituting human blood. In this study, we performed a genome-wide transcriptomic analysis of protein-coding genes in sorted blood immune cell populations to characterize the expression levels of each individual gene across the blood cell types. All data are presented in an interactive, open-access Blood Atlas as part of the Human Protein Atlas and are integrated with expression profiles across all major tissues to provide spatial classification of all protein-coding genes. This allows for a genome-wide exploration of the expression profiles across human immune cell populations and all major human tissues and organs.
  

• 1.

  Agudelo, L. Z., Ferreira, D. M., Cervenka, I., Bryzgalova, G., Dadvar, S., Jannig, P. R., Pettersson-Klein, A. T., Lakshmikanth, T., Sustarsic, E. G., Porsmyr-Palmertz, M., Correia, J. C., Izadi, M., Martínez-Redondo, V., Ueland, P. M., Midttun, Øivind, Gerhart-Hines, Z., Brodin, P., Pereira, T., Berggren, P.-O., and Ruas, J. L. (2018) Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation, Cell Metabolism 27, 378 – 392.e5.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Summary The role of tryptophan-kynurenine metabolism in psychiatric disease is well established, but remains less explored in peripheral tissues. Exercise training activates kynurenine biotransformation in skeletal muscle, which protects from neuroinflammation and leads to peripheral kynurenic acid accumulation. Here we show that kynurenic acid increases energy utilization by activating G protein-coupled receptor Gpr35, which stimulates lipid metabolism, thermogenic, and anti-inflammatory gene expression in adipose tissue. This suppresses weight gain in animals fed a high-fat diet and improves glucose tolerance. Kynurenic acid and Gpr35 enhance Pgc-1α1 expression and cellular respiration, and increase the levels of Rgs14 in adipocytes, which leads to enhanced beta-adrenergic receptor signaling. Conversely, genetic deletion of Gpr35 causes progressive weight gain and glucose intolerance, and sensitizes to the effects of high-fat diets. Finally, exercise-induced adipose tissue browning is compromised in Gpr35 knockout animals. This work uncovers kynurenine metabolism as a pathway with therapeutic potential to control energy homeostasis.

  @article{AGUDELO2018378,
  abstract = {Summary The role of tryptophan-kynurenine metabolism in psychiatric disease is well established, but remains less explored in peripheral tissues. Exercise training activates kynurenine biotransformation in skeletal muscle, which protects from neuroinflammation and leads to peripheral kynurenic acid accumulation. Here we show that kynurenic acid increases energy utilization by activating G protein-coupled receptor Gpr35, which stimulates lipid metabolism, thermogenic, and anti-inflammatory gene expression in adipose tissue. This suppresses weight gain in animals fed a high-fat diet and improves glucose tolerance. Kynurenic acid and Gpr35 enhance Pgc-1α1 expression and cellular respiration, and increase the levels of Rgs14 in adipocytes, which leads to enhanced beta-adrenergic receptor signaling. Conversely, genetic deletion of Gpr35 causes progressive weight gain and glucose intolerance, and sensitizes to the effects of high-fat diets. Finally, exercise-induced adipose tissue browning is compromised in Gpr35 knockout animals. This work uncovers kynurenine metabolism as a pathway with therapeutic potential to control energy homeostasis.},
  author = {Agudelo, Leandro Z. and Ferreira, Duarte M.S. and Cervenka, Igor and Bryzgalova, Galyna and Dadvar, Shamim and Jannig, Paulo R. and Pettersson-Klein, Amanda T. and Lakshmikanth, Tadepally and Sustarsic, Elahu G. and Porsmyr-Palmertz, Margareta and Correia, Jorge C. and Izadi, Manizheh and Martínez-Redondo, Vicente and Ueland, Per M. and Midttun, Øivind and Gerhart-Hines, Zachary and Brodin, Petter and Pereira, Teresa and Berggren, Per-Olof and Ruas, Jorge L.},
  journal = {Cell Metabolism},
  keywords = {Adipose Inflammation, tissue},
  number = 2,
  pages = {378 - 392.e5},
  title = {Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation},
  volume = 27,
  year = 2018
  }
  

  %0 Journal Article
  %1 AGUDELO2018378
  %A Agudelo, Leandro Z.
  %A Ferreira, Duarte M.S.
  %A Cervenka, Igor
  %A Bryzgalova, Galyna
  %A Dadvar, Shamim
  %A Jannig, Paulo R.
  %A Pettersson-Klein, Amanda T.
  %A Lakshmikanth, Tadepally
  %A Sustarsic, Elahu G.
  %A Porsmyr-Palmertz, Margareta
  %A Correia, Jorge C.
  %A Izadi, Manizheh
  %A Martínez-Redondo, Vicente
  %A Ueland, Per M.
  %A Midttun, Øivind
  %A Gerhart-Hines, Zachary
  %A Brodin, Petter
  %A Pereira, Teresa
  %A Berggren, Per-Olof
  %A Ruas, Jorge L.
  %D 2018
  %J Cell Metabolism
  %N 2
  %P 378 - 392.e5
  %R https://doi.org/10.1016/j.cmet.2018.01.004
  %T Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation
  %U http://www.sciencedirect.com/science/article/pii/S1550413118300536
  %V 27
  %X Summary The role of tryptophan-kynurenine metabolism in psychiatric disease is well established, but remains less explored in peripheral tissues. Exercise training activates kynurenine biotransformation in skeletal muscle, which protects from neuroinflammation and leads to peripheral kynurenic acid accumulation. Here we show that kynurenic acid increases energy utilization by activating G protein-coupled receptor Gpr35, which stimulates lipid metabolism, thermogenic, and anti-inflammatory gene expression in adipose tissue. This suppresses weight gain in animals fed a high-fat diet and improves glucose tolerance. Kynurenic acid and Gpr35 enhance Pgc-1α1 expression and cellular respiration, and increase the levels of Rgs14 in adipocytes, which leads to enhanced beta-adrenergic receptor signaling. Conversely, genetic deletion of Gpr35 causes progressive weight gain and glucose intolerance, and sensitizes to the effects of high-fat diets. Finally, exercise-induced adipose tissue browning is compromised in Gpr35 knockout animals. This work uncovers kynurenine metabolism as a pathway with therapeutic potential to control energy homeostasis.
  

• 1.

  Ju, C.-H., Blum, L. K., Kongpachith, S., Lingampalli, N., Mao, R., Brodin, P., Dekker, C. L., Davis, M. M., and Robinson, W. H. (2018) Plasmablast antibody repertoires in elderly influenza vaccine responders exhibit restricted diversity but increased breadth of binding across influenza strains, Clinical Immunology 193, 70–79.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Seasonal influenza vaccines elicit antibody responses that can prevent infection, but their efficacy is reduced in the elderly. While a subset of elderly individuals can still mount sufficient vaccine-induced antibody responses, little is known about the properties of the vaccine-induced antibody repertoires in elderly as compared to young responders. To gain insights into the effects of aging on influenza vaccine-induced antibody responses, we used flow cytometry and a cell-barcoding method to sequence antibody heavy and light chain gene pairs expressed by individual blood plasmablasts generated in response to influenza vaccination in elderly (aged 70–89) and young (aged 20–29) responders. We found similar blood plasmablast levels in the elderly and young responders seven days post vaccination. Informatics analysis revealed increased clonality, but similar heavy chain V(D)J gene usage in the elderly as compared to young vaccine responders. Although the elderly responders exhibited decreased antibody sequence diversity and fewer consequential mutations relative to young responders, recombinant antibodies from elderly responders bound a broader range of influenza strain HAs. Thus elderly influenza vaccine responders mount plasmablast responses with restricted diversity but with an increased breadth of binding across influenza strains. Our results suggest that the ability to generate plasmablast responses encoding cross-strain binding antibodies likely represents a mechanism important to vaccine responses in the elderly.

  @article{JU201870,
  abstract = {Seasonal influenza vaccines elicit antibody responses that can prevent infection, but their efficacy is reduced in the elderly. While a subset of elderly individuals can still mount sufficient vaccine-induced antibody responses, little is known about the properties of the vaccine-induced antibody repertoires in elderly as compared to young responders. To gain insights into the effects of aging on influenza vaccine-induced antibody responses, we used flow cytometry and a cell-barcoding method to sequence antibody heavy and light chain gene pairs expressed by individual blood plasmablasts generated in response to influenza vaccination in elderly (aged 70–89) and young (aged 20–29) responders. We found similar blood plasmablast levels in the elderly and young responders seven days post vaccination. Informatics analysis revealed increased clonality, but similar heavy chain V(D)J gene usage in the elderly as compared to young vaccine responders. Although the elderly responders exhibited decreased antibody sequence diversity and fewer consequential mutations relative to young responders, recombinant antibodies from elderly responders bound a broader range of influenza strain HAs. Thus elderly influenza vaccine responders mount plasmablast responses with restricted diversity but with an increased breadth of binding across influenza strains. Our results suggest that the ability to generate plasmablast responses encoding cross-strain binding antibodies likely represents a mechanism important to vaccine responses in the elderly.},
  author = {Ju, Chia-Hsin and Blum, Lisa K. and Kongpachith, Sarah and Lingampalli, Nithya and Mao, Rong and Brodin, Petter and Dekker, Cornelia L. and Davis, Mark M. and Robinson, William H.},
  journal = {Clinical Immunology},
  keywords = {vaccine},
  pages = {70 - 79},
  title = {Plasmablast antibody repertoires in elderly influenza vaccine responders exhibit restricted diversity but increased breadth of binding across influenza strains},
  volume = 193,
  year = 2018
  }
  

  %0 Journal Article
  %1 JU201870
  %A Ju, Chia-Hsin
  %A Blum, Lisa K.
  %A Kongpachith, Sarah
  %A Lingampalli, Nithya
  %A Mao, Rong
  %A Brodin, Petter
  %A Dekker, Cornelia L.
  %A Davis, Mark M.
  %A Robinson, William H.
  %D 2018
  %J Clinical Immunology
  %P 70 - 79
  %R https://doi.org/10.1016/j.clim.2018.01.011
  %T Plasmablast antibody repertoires in elderly influenza vaccine responders exhibit restricted diversity but increased breadth of binding across influenza strains
  %U http://www.sciencedirect.com/science/article/pii/S1521661618300445
  %V 193
  %X Seasonal influenza vaccines elicit antibody responses that can prevent infection, but their efficacy is reduced in the elderly. While a subset of elderly individuals can still mount sufficient vaccine-induced antibody responses, little is known about the properties of the vaccine-induced antibody repertoires in elderly as compared to young responders. To gain insights into the effects of aging on influenza vaccine-induced antibody responses, we used flow cytometry and a cell-barcoding method to sequence antibody heavy and light chain gene pairs expressed by individual blood plasmablasts generated in response to influenza vaccination in elderly (aged 70–89) and young (aged 20–29) responders. We found similar blood plasmablast levels in the elderly and young responders seven days post vaccination. Informatics analysis revealed increased clonality, but similar heavy chain V(D)J gene usage in the elderly as compared to young vaccine responders. Although the elderly responders exhibited decreased antibody sequence diversity and fewer consequential mutations relative to young responders, recombinant antibodies from elderly responders bound a broader range of influenza strain HAs. Thus elderly influenza vaccine responders mount plasmablast responses with restricted diversity but with an increased breadth of binding across influenza strains. Our results suggest that the ability to generate plasmablast responses encoding cross-strain binding antibodies likely represents a mechanism important to vaccine responses in the elderly.
  

• 1.

  Chen, Y., Lakshmikanth, T., Olin, A., Mikes, J., Remberger, M., and Brodin, P. (2018) Continuous Immune Cell Differentiation Inferred From Single-Cell Measurements Following Allogeneic Stem Cell Transplantation, Frontiers in Molecular Biosciences, Frontiers Media SA 5, 81.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  The process of immune system regeneration after allogeneic stem cell transplantation is slow, complex, and insufficiently understood. An entire immune system with all of its cell populations must regenerate from infused donor hematopoietic stem cells over the course of weeks and months post-transplantation. Both innate and adaptive arms of the immune system differ in their capacity and speed to reconstitiute in the recipient, which contributes to inadequacy in global immunity during the delayed reconstitution period. Systems-level analyses of immune systems in human patients have been made possible by high-throughput and high-dimensional, state-of-the-art, single-cell methodologies such as mass cytometry. Mass cytometry has revolutionized our ability to comprehensively profile all immune cell populations simultaneously in blood or tissue samples, providing signatures of differentially regulated cells in a range of clinical conditions. Such kind of systems immunology analyses promise not only for more accurate descriptions of variation between patients but also within individual patients over time, inter-dependencies between cell populations and the inference of developmental trajectories for specific cell populations. Here, we took advantage of a recently performed longitudinal mass cytometry analysis in 26 patients with hematological malignancies followed during the first 12 months following allogeneic stem cell transplantation. We present a proof-of-principle analysis to understand the evolution of individual immune cell populations. By applying non-linear dimensionality reduction and feauture extraction algorithms, we infer trajectories for individual immune cell populations, and map continuous marker expression changes occuring during immune cell regeneration that add novel information about this developmental process.

  @article{Chen_2018,
  abstract = {The process of immune system regeneration after allogeneic stem cell transplantation is slow, complex, and insufficiently understood. An entire immune system with all of its cell populations must regenerate from infused donor hematopoietic stem cells over the course of weeks and months post-transplantation. Both innate and adaptive arms of the immune system differ in their capacity and speed to reconstitiute in the recipient, which contributes to inadequacy in global immunity during the delayed reconstitution period. Systems-level analyses of immune systems in human patients have been made possible by high-throughput and high-dimensional, state-of-the-art, single-cell methodologies such as mass cytometry. Mass cytometry has revolutionized our ability to comprehensively profile all immune cell populations simultaneously in blood or tissue samples, providing signatures of differentially regulated cells in a range of clinical conditions. Such kind of systems immunology analyses promise not only for more accurate descriptions of variation between patients but also within individual patients over time, inter-dependencies between cell populations and the inference of developmental trajectories for specific cell populations. Here, we took advantage of a recently performed longitudinal mass cytometry analysis in 26 patients with hematological malignancies followed during the first 12 months following allogeneic stem cell transplantation. We present a proof-of-principle analysis to understand the evolution of individual immune cell populations. By applying non-linear dimensionality reduction and feauture extraction algorithms, we infer trajectories for individual immune cell populations, and map continuous marker expression changes occuring during immune cell regeneration that add novel information about this developmental process.},
  author = {Chen, Yang and Lakshmikanth, Tadepally and Olin, Axel and Mikes, Jaromir and Remberger, Mats and Brodin, Petter},
  journal = {Frontiers in Molecular Biosciences},
  keywords = {ASCT},
  month = {sep},
  pages = 81,
  publisher = {Frontiers Media SA},
  title = {Continuous Immune Cell Differentiation Inferred From Single-Cell Measurements Following Allogeneic Stem Cell Transplantation},
  volume = 5,
  year = 2018
  }
  

  %0 Journal Article
  %1 Chen_2018
  %A Chen, Yang
  %A Lakshmikanth, Tadepally
  %A Olin, Axel
  %A Mikes, Jaromir
  %A Remberger, Mats
  %A Brodin, Petter
  %D 2018
  %I Frontiers Media SA
  %J Frontiers in Molecular Biosciences
  %P 81
  %R 10.3389/fmolb.2018.00081
  %T Continuous Immune Cell Differentiation Inferred From Single-Cell Measurements Following Allogeneic Stem Cell Transplantation
  %U https://doi.org/10.3389%2Ffmolb.2018.00081
  %V 5
  %X The process of immune system regeneration after allogeneic stem cell transplantation is slow, complex, and insufficiently understood. An entire immune system with all of its cell populations must regenerate from infused donor hematopoietic stem cells over the course of weeks and months post-transplantation. Both innate and adaptive arms of the immune system differ in their capacity and speed to reconstitiute in the recipient, which contributes to inadequacy in global immunity during the delayed reconstitution period. Systems-level analyses of immune systems in human patients have been made possible by high-throughput and high-dimensional, state-of-the-art, single-cell methodologies such as mass cytometry. Mass cytometry has revolutionized our ability to comprehensively profile all immune cell populations simultaneously in blood or tissue samples, providing signatures of differentially regulated cells in a range of clinical conditions. Such kind of systems immunology analyses promise not only for more accurate descriptions of variation between patients but also within individual patients over time, inter-dependencies between cell populations and the inference of developmental trajectories for specific cell populations. Here, we took advantage of a recently performed longitudinal mass cytometry analysis in 26 patients with hematological malignancies followed during the first 12 months following allogeneic stem cell transplantation. We present a proof-of-principle analysis to understand the evolution of individual immune cell populations. By applying non-linear dimensionality reduction and feauture extraction algorithms, we infer trajectories for individual immune cell populations, and map continuous marker expression changes occuring during immune cell regeneration that add novel information about this developmental process.
  

• 1.

  Ganesan, S., Luu, T. T., Chambers, B., Meinke, S., Brodin, P., Vivier, E., Wetzel, D. M., Koleske, A. J., Kadri, N., and Höglund, P. (2017) The Abl-1 Kinase is Dispensable for NK Cell Inhibitory Signalling and is not Involved in Murine NK Cell Education., Scandinavian journal of immunology 86, 135–142.

  AbstractBibTeXEndNoteDOIBibSonomy

  Natural killer (NK) cell responsiveness in the mouse is determined in an education process guided by inhibitory Ly49 and NKG2A receptors binding to MHC class I molecules. It has been proposed that inhibitory signalling in human NK cells involves Abl-1 (c-Abl)-mediated phosphorylation of Crk, lowering NK cell function via disruption of a signalling complex including C3G and c-Cbl, suggesting that NK cell education might involve c-Abl. Mice deficient in c-Abl expression specifically in murine NK cells displayed normal inhibitory and activating receptor repertoires. Furthermore, c-Abl-deficient NK cells fluxed Ca2+ normally after triggering of ITAM receptors, killed YAC-1 tumour cells efficiently and showed normal, or even slightly elevated, capacity to produce IFN-γ after activating receptor stimulation. Consistent with these results, c-Abl deficiency in NK cells did not affect NK cell inhibition via the receptors Ly49G2, Ly49A and NKG2A. We conclude that signalling downstream of murine inhibitory receptors does not involve c-Abl and that c-Abl plays no major role in NK cell education in the mouse.

  @article{noauthororeditor,
  abstract = {Natural killer (NK) cell responsiveness in the mouse is determined in an education process guided by inhibitory Ly49 and NKG2A receptors binding to MHC class I molecules. It has been proposed that inhibitory signalling in human NK cells involves Abl-1 (c-Abl)-mediated phosphorylation of Crk, lowering NK cell function via disruption of a signalling complex including C3G and c-Cbl, suggesting that NK cell education might involve c-Abl. Mice deficient in c-Abl expression specifically in murine NK cells displayed normal inhibitory and activating receptor repertoires. Furthermore, c-Abl-deficient NK cells fluxed Ca2+ normally after triggering of ITAM receptors, killed YAC-1 tumour cells efficiently and showed normal, or even slightly elevated, capacity to produce IFN-γ after activating receptor stimulation. Consistent with these results, c-Abl deficiency in NK cells did not affect NK cell inhibition via the receptors Ly49G2, Ly49A and NKG2A. We conclude that signalling downstream of murine inhibitory receptors does not involve c-Abl and that c-Abl plays no major role in NK cell education in the mouse.},
  author = {Ganesan, Sridharan and Luu, Thuy Thanh and Chambers, BJ and Meinke, Stephan and Brodin, Petter and Vivier, Eric and Wetzel, Dawn M and Koleske, Anthony J and Kadri, Nadir and Höglund, Petter},
  journal = {Scandinavian journal of immunology},
  keywords = {NK},
  month = {September},
  number = 3,
  pages = {135-142},
  title = {The Abl-1 Kinase is Dispensable for NK Cell Inhibitory Signalling and is not Involved in Murine NK Cell Education.},
  volume = 86,
  year = 2017
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Ganesan, Sridharan
  %A Luu, Thuy Thanh
  %A Chambers, BJ
  %A Meinke, Stephan
  %A Brodin, Petter
  %A Vivier, Eric
  %A Wetzel, Dawn M
  %A Koleske, Anthony J
  %A Kadri, Nadir
  %A Höglund, Petter
  %D 2017
  %J Scandinavian journal of immunology
  %N 3
  %P 135-142
  %R 10.1111/sji.12574
  %T The Abl-1 Kinase is Dispensable for NK Cell Inhibitory Signalling and is not Involved in Murine NK Cell Education.
  %V 86
  %X Natural killer (NK) cell responsiveness in the mouse is determined in an education process guided by inhibitory Ly49 and NKG2A receptors binding to MHC class I molecules. It has been proposed that inhibitory signalling in human NK cells involves Abl-1 (c-Abl)-mediated phosphorylation of Crk, lowering NK cell function via disruption of a signalling complex including C3G and c-Cbl, suggesting that NK cell education might involve c-Abl. Mice deficient in c-Abl expression specifically in murine NK cells displayed normal inhibitory and activating receptor repertoires. Furthermore, c-Abl-deficient NK cells fluxed Ca2+ normally after triggering of ITAM receptors, killed YAC-1 tumour cells efficiently and showed normal, or even slightly elevated, capacity to produce IFN-γ after activating receptor stimulation. Consistent with these results, c-Abl deficiency in NK cells did not affect NK cell inhibition via the receptors Ly49G2, Ly49A and NKG2A. We conclude that signalling downstream of murine inhibitory receptors does not involve c-Abl and that c-Abl plays no major role in NK cell education in the mouse.
  

• 1.

  Brodin, P. (2017) Life-Saving Degeneracy in the Human Immune System, Cell Host & Microbe 21, 309–310.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Different human immune system components coordinate to ensure effective control of pathogens. Israel et al. (2017) examine the immune system of a patient with an inborn genetic error, presenting as impaired TLR signaling and staphylococcal disease, and uncover a beautiful example of degeneracy between innate and adaptive branches of immunity.

  @article{BRODIN2017309,
  abstract = {Different human immune system components coordinate to ensure effective control of pathogens. Israel et al. (2017) examine the immune system of a patient with an inborn genetic error, presenting as impaired TLR signaling and staphylococcal disease, and uncover a beautiful example of degeneracy between innate and adaptive branches of immunity.},
  author = {Brodin, Petter},
  journal = {Cell Host & Microbe},
  keywords = {immune system},
  month = {March},
  number = 3,
  pages = {309 - 310},
  title = {Life-Saving Degeneracy in the Human Immune System},
  volume = 21,
  year = 2017
  }
  

  %0 Journal Article
  %1 BRODIN2017309
  %A Brodin, Petter
  %D 2017
  %J Cell Host & Microbe
  %N 3
  %P 309 - 310
  %R https://doi.org/10.1016/j.chom.2017.02.018
  %T Life-Saving Degeneracy in the Human Immune System
  %U http://www.sciencedirect.com/science/article/pii/S193131281730080X
  %V 21
  %X Different human immune system components coordinate to ensure effective control of pathogens. Israel et al. (2017) examine the immune system of a patient with an inborn genetic error, presenting as impaired TLR signaling and staphylococcal disease, and uncover a beautiful example of degeneracy between innate and adaptive branches of immunity.
  

• 1.

  Kaiser, Y., Lakshmikanth, T., Chen, Y., Mikes, J., Eklund, A., Brodin, P., Achour, A., and Grunewald, J. (2017) Mass Cytometry Identifies Distinct Lung CD4\($\mathplus$\) T Cell Patterns in Löfgren’s Syndrome and Non-Löfgren’s Syndrome Sarcoidosis, Frontiers in Immunology, Frontiers Media SA 8, 1130.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Sarcoidosis is a granulomatous disorder of unknown etiology, characterized by accumulation of activated CD4+ T cells in the lungs. Disease phenotypes Löfgren's syndrome (LS) and "non-LS" differ in terms of clinical manifestations, genetic background, HLA association, and prognosis, but the underlying inflammatory mechanisms largely remain unknown. Bronchoalveolar lavage fluid cells from four HLA-DRB1*03+ LS and four HLA-DRB1*03- non-LS patients were analyzed by mass cytometry, using a panel of 33 unique markers. Differentially regulated CD4+ T cell populations were identified using the Citrus algorithm, and t-stochastic neighborhood embedding was applied for dimensionality reduction and single-cell data visualization. We identified 19 individual CD4+ T cell clusters differing significantly in abundance between LS and non-LS patients. Seven clusters more frequent in LS patients were characterized by significantly higher expression of regulatory receptors CTLA-4, PD-1, and ICOS, along with low expression of adhesion marker CD44. In contrast, 12 clusters primarily found in non-LS displayed elevated expression of activation and effector markers HLA-DR, CD127, CD39, as well as CD44. Hierarchical clustering further indicated functional heterogeneity and diverse origins of T cell receptor Vα2.3/Vβ22-restricted cells in LS. Finally, a near-complete overlap of CD8 and Ki-67 expression suggested larger influence of CD8+ T cell activity on sarcoid inflammation than previously appreciated. In this study, we provide detailed characterization of pulmonary T cells and immunological parameters that define separate disease pathways in LS and non-LS. With direct association to clinical parameters, such as granuloma persistence, resolution, or chronic inflammation, these results provide a valuable foundation for further exploration and potential clinical application.

  @article{Kaiser_2017,
  abstract = {Sarcoidosis is a granulomatous disorder of unknown etiology, characterized by accumulation of activated CD4+ T cells in the lungs. Disease phenotypes Löfgren's syndrome (LS) and "non-LS" differ in terms of clinical manifestations, genetic background, HLA association, and prognosis, but the underlying inflammatory mechanisms largely remain unknown. Bronchoalveolar lavage fluid cells from four HLA-DRB1*03+ LS and four HLA-DRB1*03- non-LS patients were analyzed by mass cytometry, using a panel of 33 unique markers. Differentially regulated CD4+ T cell populations were identified using the Citrus algorithm, and t-stochastic neighborhood embedding was applied for dimensionality reduction and single-cell data visualization. We identified 19 individual CD4+ T cell clusters differing significantly in abundance between LS and non-LS patients. Seven clusters more frequent in LS patients were characterized by significantly higher expression of regulatory receptors CTLA-4, PD-1, and ICOS, along with low expression of adhesion marker CD44. In contrast, 12 clusters primarily found in non-LS displayed elevated expression of activation and effector markers HLA-DR, CD127, CD39, as well as CD44. Hierarchical clustering further indicated functional heterogeneity and diverse origins of T cell receptor Vα2.3/Vβ22-restricted cells in LS. Finally, a near-complete overlap of CD8 and Ki-67 expression suggested larger influence of CD8+ T cell activity on sarcoid inflammation than previously appreciated. In this study, we provide detailed characterization of pulmonary T cells and immunological parameters that define separate disease pathways in LS and non-LS. With direct association to clinical parameters, such as granuloma persistence, resolution, or chronic inflammation, these results provide a valuable foundation for further exploration and potential clinical application.},
  author = {Kaiser, Ylva and Lakshmikanth, Tadepally and Chen, Yang and Mikes, Jaromir and Eklund, Anders and Brodin, Petter and Achour, Adnane and Grunewald, Johan},
  journal = {Frontiers in Immunology},
  keywords = {cytometry mass},
  month = {sep},
  pages = 1130,
  publisher = {Frontiers Media SA},
  title = {Mass Cytometry Identifies Distinct Lung CD4\($\mathplus$\) T Cell Patterns in Löfgren's Syndrome and Non-Löfgren's Syndrome Sarcoidosis},
  volume = 8,
  year = 2017
  }
  

  %0 Journal Article
  %1 Kaiser_2017
  %A Kaiser, Ylva
  %A Lakshmikanth, Tadepally
  %A Chen, Yang
  %A Mikes, Jaromir
  %A Eklund, Anders
  %A Brodin, Petter
  %A Achour, Adnane
  %A Grunewald, Johan
  %D 2017
  %I Frontiers Media SA
  %J Frontiers in Immunology
  %P 1130
  %R 10.3389/fimmu.2017.01130
  %T Mass Cytometry Identifies Distinct Lung CD4\($\mathplus$\) T Cell Patterns in Löfgren's Syndrome and Non-Löfgren's Syndrome Sarcoidosis
  %U https://doi.org/10.3389%2Ffimmu.2017.01130
  %V 8
  %X Sarcoidosis is a granulomatous disorder of unknown etiology, characterized by accumulation of activated CD4+ T cells in the lungs. Disease phenotypes Löfgren's syndrome (LS) and "non-LS" differ in terms of clinical manifestations, genetic background, HLA association, and prognosis, but the underlying inflammatory mechanisms largely remain unknown. Bronchoalveolar lavage fluid cells from four HLA-DRB1*03+ LS and four HLA-DRB1*03- non-LS patients were analyzed by mass cytometry, using a panel of 33 unique markers. Differentially regulated CD4+ T cell populations were identified using the Citrus algorithm, and t-stochastic neighborhood embedding was applied for dimensionality reduction and single-cell data visualization. We identified 19 individual CD4+ T cell clusters differing significantly in abundance between LS and non-LS patients. Seven clusters more frequent in LS patients were characterized by significantly higher expression of regulatory receptors CTLA-4, PD-1, and ICOS, along with low expression of adhesion marker CD44. In contrast, 12 clusters primarily found in non-LS displayed elevated expression of activation and effector markers HLA-DR, CD127, CD39, as well as CD44. Hierarchical clustering further indicated functional heterogeneity and diverse origins of T cell receptor Vα2.3/Vβ22-restricted cells in LS. Finally, a near-complete overlap of CD8 and Ki-67 expression suggested larger influence of CD8+ T cell activity on sarcoid inflammation than previously appreciated. In this study, we provide detailed characterization of pulmonary T cells and immunological parameters that define separate disease pathways in LS and non-LS. With direct association to clinical parameters, such as granuloma persistence, resolution, or chronic inflammation, these results provide a valuable foundation for further exploration and potential clinical application.
  

• 1.

  Stikvoort, A., Chen, Y., Raadestad, E., Törlén, J., Lakshmikanth, T., Björklund, A., Mikes, J., Achour, A., Gertow, J., Sundberg, B., Remberger, M., Sundin, M., Mattsson, J., Brodin, P., and Uhlin, M. (2017) Combining Flow and Mass Cytometry in the Search for Biomarkers in Chronic Graft-versus-Host Disease, Frontiers in Immunology, Frontiers Media SA 8, 717.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Chronic graft-versus-host disease (cGVHD) is a debilitating complication arising in around half of all patients treated with an allogeneic hematopoietic stem cell transplantation. Even though treatment of severe cGVHD has improved during recent years, it remains one of the main causes of morbidity and mortality in affected patients. Biomarkers in blood that could aid in the diagnosis and classification of cGVHD severity are needed for the development of novel treatment strategies that can alleviate symptoms and reduce the need for painful and sometimes complicated tissue biopsies. Methods that comprehensively profile complex biological systems such as the immune system can reveal unanticipated markers when used with the appropriate methods of data analysis. Here, we used mass cytometry, flow cytometry, enzyme-linked immunosorbent assay, and multiplex assays to systematically profile immune cell populations in 68 patients with varying grades of cGVHD. We identified multiple subpopulations across T, B, and NK-cell lineages that distinguished patients with cGVHD from those without cGVHD and which were associated in varying ways with severity of cGVHD. Specifically, initial flow cytometry demonstrated that patients with more severe cGVHD had lower mucosal-associated T cell frequencies, with a concomitant higher level of CD38 expression on T cells. Mass cytometry could identify unique subpopulations specific for cGVHD severity albeit with some seemingly conflicting results. For instance, patients with severe cGVHD had an increased frequency of activated B cells compared to patients with moderate cGVHD while activated B cells were found at a reduced frequency in patients with mild cGVHD compared to patients without cGVHD. Moreover, results indicate it may be possible to validate mass cytometry results with clinically viable, smaller flow cytometry panels. Finally, no differences in levels of blood soluble markers could be identified, with the exception for the semi-soluble combined marker B-cell activating factor/B cell ratio, which was increased in patients with mild cGVHD compared to patients without cGVHD. These findings suggest that interdependencies between such perturbed subpopulations of cells play a role in cGVHD pathogenesis and can serve as future diagnostic and therapeutic targets.

  @article{Stikvoort_2017,
  abstract = {Chronic graft-versus-host disease (cGVHD) is a debilitating complication arising in around half of all patients treated with an allogeneic hematopoietic stem cell transplantation. Even though treatment of severe cGVHD has improved during recent years, it remains one of the main causes of morbidity and mortality in affected patients. Biomarkers in blood that could aid in the diagnosis and classification of cGVHD severity are needed for the development of novel treatment strategies that can alleviate symptoms and reduce the need for painful and sometimes complicated tissue biopsies. Methods that comprehensively profile complex biological systems such as the immune system can reveal unanticipated markers when used with the appropriate methods of data analysis. Here, we used mass cytometry, flow cytometry, enzyme-linked immunosorbent assay, and multiplex assays to systematically profile immune cell populations in 68 patients with varying grades of cGVHD. We identified multiple subpopulations across T, B, and NK-cell lineages that distinguished patients with cGVHD from those without cGVHD and which were associated in varying ways with severity of cGVHD. Specifically, initial flow cytometry demonstrated that patients with more severe cGVHD had lower mucosal-associated T cell frequencies, with a concomitant higher level of CD38 expression on T cells. Mass cytometry could identify unique subpopulations specific for cGVHD severity albeit with some seemingly conflicting results. For instance, patients with severe cGVHD had an increased frequency of activated B cells compared to patients with moderate cGVHD while activated B cells were found at a reduced frequency in patients with mild cGVHD compared to patients without cGVHD. Moreover, results indicate it may be possible to validate mass cytometry results with clinically viable, smaller flow cytometry panels. Finally, no differences in levels of blood soluble markers could be identified, with the exception for the semi-soluble combined marker B-cell activating factor/B cell ratio, which was increased in patients with mild cGVHD compared to patients without cGVHD. These findings suggest that interdependencies between such perturbed subpopulations of cells play a role in cGVHD pathogenesis and can serve as future diagnostic and therapeutic targets.},
  author = {Stikvoort, Arwen and Chen, Yang and Raadestad, Emelie and Törlén, Johan and Lakshmikanth, Tadepally and Björklund, Andreas and Mikes, Jaromir and Achour, Adnane and Gertow, Jens and Sundberg, Berit and Remberger, Mats and Sundin, Mikael and Mattsson, Jonas and Brodin, Petter and Uhlin, Michael},
  journal = {Frontiers in Immunology},
  keywords = {Cytometry Mass},
  month = {June},
  pages = 717,
  publisher = {Frontiers Media SA},
  title = {Combining Flow and Mass Cytometry in the Search for Biomarkers in Chronic Graft-versus-Host Disease},
  volume = 8,
  year = 2017
  }
  

  %0 Journal Article
  %1 Stikvoort_2017
  %A Stikvoort, Arwen
  %A Chen, Yang
  %A Raadestad, Emelie
  %A Törlén, Johan
  %A Lakshmikanth, Tadepally
  %A Björklund, Andreas
  %A Mikes, Jaromir
  %A Achour, Adnane
  %A Gertow, Jens
  %A Sundberg, Berit
  %A Remberger, Mats
  %A Sundin, Mikael
  %A Mattsson, Jonas
  %A Brodin, Petter
  %A Uhlin, Michael
  %D 2017
  %I Frontiers Media SA
  %J Frontiers in Immunology
  %P 717
  %R 10.3389/fimmu.2017.00717
  %T Combining Flow and Mass Cytometry in the Search for Biomarkers in Chronic Graft-versus-Host Disease
  %U https://doi.org/10.3389%2Ffimmu.2017.00717
  %V 8
  %X Chronic graft-versus-host disease (cGVHD) is a debilitating complication arising in around half of all patients treated with an allogeneic hematopoietic stem cell transplantation. Even though treatment of severe cGVHD has improved during recent years, it remains one of the main causes of morbidity and mortality in affected patients. Biomarkers in blood that could aid in the diagnosis and classification of cGVHD severity are needed for the development of novel treatment strategies that can alleviate symptoms and reduce the need for painful and sometimes complicated tissue biopsies. Methods that comprehensively profile complex biological systems such as the immune system can reveal unanticipated markers when used with the appropriate methods of data analysis. Here, we used mass cytometry, flow cytometry, enzyme-linked immunosorbent assay, and multiplex assays to systematically profile immune cell populations in 68 patients with varying grades of cGVHD. We identified multiple subpopulations across T, B, and NK-cell lineages that distinguished patients with cGVHD from those without cGVHD and which were associated in varying ways with severity of cGVHD. Specifically, initial flow cytometry demonstrated that patients with more severe cGVHD had lower mucosal-associated T cell frequencies, with a concomitant higher level of CD38 expression on T cells. Mass cytometry could identify unique subpopulations specific for cGVHD severity albeit with some seemingly conflicting results. For instance, patients with severe cGVHD had an increased frequency of activated B cells compared to patients with moderate cGVHD while activated B cells were found at a reduced frequency in patients with mild cGVHD compared to patients without cGVHD. Moreover, results indicate it may be possible to validate mass cytometry results with clinically viable, smaller flow cytometry panels. Finally, no differences in levels of blood soluble markers could be identified, with the exception for the semi-soluble combined marker B-cell activating factor/B cell ratio, which was increased in patients with mild cGVHD compared to patients without cGVHD. These findings suggest that interdependencies between such perturbed subpopulations of cells play a role in cGVHD pathogenesis and can serve as future diagnostic and therapeutic targets.
  

• 1.

  Kaczorowski, K. J., Shekhar, K., Nkulikiyimfura, D., Dekker, C. L., Maecker, H., Davis, M., Chakraborty, A. K., and Brodin, P. (2017) Continuous immunotypes describe human immune variation and predict diverse responses., Proceedings of the National Academy of Sciences of the United States of America 114, 1091–6490.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Kaczorowski, Kevin J and Shekhar, Karthik and Nkulikiyimfura, Dieudonné and Dekker, Cornelia L and Maecker, Holden and Davis, MM and Chakraborty, Arup K and Brodin, Petter},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {human immune variation},
  month = {July},
  number = 30,
  pages = {1091-6490},
  title = {Continuous immunotypes describe human immune variation and predict diverse responses.},
  volume = 114,
  year = 2017
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Kaczorowski, Kevin J
  %A Shekhar, Karthik
  %A Nkulikiyimfura, Dieudonné
  %A Dekker, Cornelia L
  %A Maecker, Holden
  %A Davis, MM
  %A Chakraborty, Arup K
  %A Brodin, Petter
  %D 2017
  %J Proceedings of the National Academy of Sciences of the United States of America
  %N 30
  %P 1091-6490
  %R 10.1073/pnas.1705065114
  %T Continuous immunotypes describe human immune variation and predict diverse responses.
  %V 114
  

• 1.

  Brodin, P., and Davis, M. (2017) Human immune system variation., Nature Reviews Immunology 17, 1474–1741.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Brodin, Petter and Davis, MM},
  journal = {Nature Reviews Immunology},
  keywords = {Immune variation},
  month = {January},
  number = 1,
  pages = {1474-1741},
  title = {Human immune system variation.},
  volume = 17,
  year = 2017
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Brodin, Petter
  %A Davis, MM
  %D 2017
  %J Nature Reviews Immunology
  %N 1
  %P 1474-1741
  %R 10.1038/nri.2016.125
  %T Human immune system variation.
  %V 17
  

• 1.

  Wagner, A. K., Kadri, N., Snäll, J., Brodin, P., Gilfillan, S., Colonna, M., Bernhardt, G., Höglund, P., Kärre, K., and Chambers, B. J. (2017) Expression of CD226 is associated to but not required for NK cell education, Nature Communications 8, 15627-.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  DNAX accessory molecule-1 (DNAM-1, also known as CD226) is an activating receptor expressed on subsets of natural killer (NK) and T cells, interacts with its ligands CD155 or CD112, and has co-varied expression with inhibitory receptors. Since inhibitory receptors control NK-cell activation and are necessary for MHC-I-dependent education, we investigated whether DNAM-1 expression is also involved in NK-cell education. Here we show an MHC-I-dependent correlation between DNAM-1 expression and NK-cell education, and an association between DNAM-1 and NKG2A that occurs even in MHC class I deficient mice. DNAM-1 is expressed early during NK-cell development, precedes the expression of MHC-I-specific inhibitory receptors, and is modulated in an education-dependent fashion. Cd226−/− mice have missing self-responses and NK cells with a normal receptor repertoire. We propose a model in which NK-cell education prevents or delays downregulation of DNAM-1. This molecule endows educated NK cells with enhanced effector functions but is dispensable for education.

  @article{wagner2017expression,
  abstract = {DNAX accessory molecule-1 (DNAM-1, also known as CD226) is an activating receptor expressed on subsets of natural killer (NK) and T cells, interacts with its ligands CD155 or CD112, and has co-varied expression with inhibitory receptors. Since inhibitory receptors control NK-cell activation and are necessary for MHC-I-dependent education, we investigated whether DNAM-1 expression is also involved in NK-cell education. Here we show an MHC-I-dependent correlation between DNAM-1 expression and NK-cell education, and an association between DNAM-1 and NKG2A that occurs even in MHC class I deficient mice. DNAM-1 is expressed early during NK-cell development, precedes the expression of MHC-I-specific inhibitory receptors, and is modulated in an education-dependent fashion. Cd226−/− mice have missing self-responses and NK cells with a normal receptor repertoire. We propose a model in which NK-cell education prevents or delays downregulation of DNAM-1. This molecule endows educated NK cells with enhanced effector functions but is dispensable for education.},
  author = {Wagner, Arnika K. and Kadri, Nadir and Snäll, Johanna and Brodin, Petter and Gilfillan, Susan and Colonna, Marco and Bernhardt, Günter and Höglund, Petter and Kärre, Klas and Chambers, Benedict J.},
  journal = {Nature Communications},
  keywords = {nk},
  number = 1,
  pages = {15627--},
  title = {Expression of CD226 is associated to but not required for NK cell education},
  volume = 8,
  year = 2017
  }
  

  %0 Journal Article
  %1 wagner2017expression
  %A Wagner, Arnika K.
  %A Kadri, Nadir
  %A Snäll, Johanna
  %A Brodin, Petter
  %A Gilfillan, Susan
  %A Colonna, Marco
  %A Bernhardt, Günter
  %A Höglund, Petter
  %A Kärre, Klas
  %A Chambers, Benedict J.
  %D 2017
  %J Nature Communications
  %N 1
  %P 15627--
  %R 10.1038/ncomms15627
  %T Expression of CD226 is associated to but not required for NK cell education
  %U https://doi.org/10.1038/ncomms15627
  %V 8
  %X DNAX accessory molecule-1 (DNAM-1, also known as CD226) is an activating receptor expressed on subsets of natural killer (NK) and T cells, interacts with its ligands CD155 or CD112, and has co-varied expression with inhibitory receptors. Since inhibitory receptors control NK-cell activation and are necessary for MHC-I-dependent education, we investigated whether DNAM-1 expression is also involved in NK-cell education. Here we show an MHC-I-dependent correlation between DNAM-1 expression and NK-cell education, and an association between DNAM-1 and NKG2A that occurs even in MHC class I deficient mice. DNAM-1 is expressed early during NK-cell development, precedes the expression of MHC-I-specific inhibitory receptors, and is modulated in an education-dependent fashion. Cd226−/− mice have missing self-responses and NK cells with a normal receptor repertoire. We propose a model in which NK-cell education prevents or delays downregulation of DNAM-1. This molecule endows educated NK cells with enhanced effector functions but is dispensable for education.
  

• 1.

  Lakshmikanth, T., Olin, A., Chen, Y., Mikes, J., Fredlund, E., Remberger, M., Omazic, B., and Brodin, P. (2017) Mass Cytometry and Topological Data Analysis Reveal Immune Parameters Associated with Complications after Allogeneic Stem Cell Transplantation, Cell Reports 20, 2238–2250.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Summary Human immune systems are variable, and immune responses are often unpredictable. Systems-level analyses offer increased power to sort patients on the basis of coordinated changes across immune cells and proteins. Allogeneic stem cell transplantation is a well-established form of immunotherapy whereby a donor immune system induces a graft-versus-leukemia response. This fails when the donor immune system regenerates improperly, leaving the patient susceptible to infections and leukemia relapse. We present a systems-level analysis by mass cytometry and serum profiling in 26 patients sampled 1, 2, 3, 6, and 12 months after transplantation. Using a combination of machine learning and topological data analyses, we show that global immune signatures associated with clinical outcome can be revealed, even when patients are few and heterogeneous. This high-resolution systems immune monitoring approach holds the potential for improving the development and evaluation of immunotherapies in the future.

  @article{LAKSHMIKANTH20172238,
  abstract = {Summary Human immune systems are variable, and immune responses are often unpredictable. Systems-level analyses offer increased power to sort patients on the basis of coordinated changes across immune cells and proteins. Allogeneic stem cell transplantation is a well-established form of immunotherapy whereby a donor immune system induces a graft-versus-leukemia response. This fails when the donor immune system regenerates improperly, leaving the patient susceptible to infections and leukemia relapse. We present a systems-level analysis by mass cytometry and serum profiling in 26 patients sampled 1, 2, 3, 6, and 12 months after transplantation. Using a combination of machine learning and topological data analyses, we show that global immune signatures associated with clinical outcome can be revealed, even when patients are few and heterogeneous. This high-resolution systems immune monitoring approach holds the potential for improving the development and evaluation of immunotherapies in the future.},
  author = {Lakshmikanth, Tadepally and Olin, Axel and Chen, Yang and Mikes, Jaromir and Fredlund, Erik and Remberger, Mats and Omazic, Brigitta and Brodin, Petter},
  journal = {Cell Reports},
  keywords = {ASCT Cytometry, Mass},
  number = 9,
  pages = {2238 - 2250},
  title = {Mass Cytometry and Topological Data Analysis Reveal Immune Parameters Associated with Complications after Allogeneic Stem Cell Transplantation},
  volume = 20,
  year = 2017
  }
  

  %0 Journal Article
  %1 LAKSHMIKANTH20172238
  %A Lakshmikanth, Tadepally
  %A Olin, Axel
  %A Chen, Yang
  %A Mikes, Jaromir
  %A Fredlund, Erik
  %A Remberger, Mats
  %A Omazic, Brigitta
  %A Brodin, Petter
  %D 2017
  %J Cell Reports
  %N 9
  %P 2238 - 2250
  %R https://doi.org/10.1016/j.celrep.2017.08.021
  %T Mass Cytometry and Topological Data Analysis Reveal Immune Parameters Associated with Complications after Allogeneic Stem Cell Transplantation
  %U http://www.sciencedirect.com/science/article/pii/S2211124717311130
  %V 20
  %X Summary Human immune systems are variable, and immune responses are often unpredictable. Systems-level analyses offer increased power to sort patients on the basis of coordinated changes across immune cells and proteins. Allogeneic stem cell transplantation is a well-established form of immunotherapy whereby a donor immune system induces a graft-versus-leukemia response. This fails when the donor immune system regenerates improperly, leaving the patient susceptible to infections and leukemia relapse. We present a systems-level analysis by mass cytometry and serum profiling in 26 patients sampled 1, 2, 3, 6, and 12 months after transplantation. Using a combination of machine learning and topological data analyses, we show that global immune signatures associated with clinical outcome can be revealed, even when patients are few and heterogeneous. This high-resolution systems immune monitoring approach holds the potential for improving the development and evaluation of immunotherapies in the future.
  

• 1.

  Brodin, P. (2015) Powerful Populations Respond to Viruses and Vaccines, Immunity 43, 1035–1037.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  In this issue of Immunity, Andres-Terre et al. (2015) and Nakaya et al. (2015) perform multi-cohort meta-analyses of immune responses to viruses and vaccines. With increased statistical power and more diverse sampling populations, their findings promise to be more generally applicable and suggestive of novel mechanisms for regulating immunity.

  @article{BRODIN20151035,
  abstract = {In this issue of Immunity, Andres-Terre et al. (2015) and Nakaya et al. (2015) perform multi-cohort meta-analyses of immune responses to viruses and vaccines. With increased statistical power and more diverse sampling populations, their findings promise to be more generally applicable and suggestive of novel mechanisms for regulating immunity.},
  author = {Brodin, Petter},
  journal = {Immunity},
  keywords = {Vaccines},
  month = {December},
  number = 6,
  pages = {1035 - 1037},
  title = {Powerful Populations Respond to Viruses and Vaccines},
  volume = 43,
  year = 2015
  }
  

  %0 Journal Article
  %1 BRODIN20151035
  %A Brodin, Petter
  %D 2015
  %J Immunity
  %N 6
  %P 1035 - 1037
  %R https://doi.org/10.1016/j.immuni.2015.11.018
  %T Powerful Populations Respond to Viruses and Vaccines
  %U http://www.sciencedirect.com/science/article/pii/S1074761315004963
  %V 43
  %X In this issue of Immunity, Andres-Terre et al. (2015) and Nakaya et al. (2015) perform multi-cohort meta-analyses of immune responses to viruses and vaccines. With increased statistical power and more diverse sampling populations, their findings promise to be more generally applicable and suggestive of novel mechanisms for regulating immunity.
  

• 1.

  Gao, T., Brodin, P., Davis, M., and Jojic, V. (2015) Drug-induced mRNA signatures are enriched for the minority of genes that are highly heritable., Biocomputing 395–406.

  AbstractBibTeXEndNoteDOIBibSonomy

  The blood gene expression signatures are used as biomarkers for immunological and non- immunological diseases. Therefore, it is important to understand the variation in blood gene expression patterns and the factors (heritable/non-heritable) that underlie this variation. In this paper, we study the relationship between drug effects on the one hand, and heritable and non-heritable factors influencing gene expression on the other. Understanding of this relationship can help select appropriate targets for drugs aimed at reverting disease phenotypes to healthy states. In order to estimate heritable and non-heritable effects on gene expression, we use Twin-ACE model on a gene expression dataset MuTHER, measured in blood samples from monozygotic and dizygotic twins. In order to associate gene expression with drug effects, we use CMap database. We show that, even though the expressions of most genes are driven by non-heritable factors, drugs are more likely to influence expression of genes, driven by heritable rather than non-heritable factors. We further study this finding in the context of a gene regulatory network. We investigate the relationship between the drug effects on gene expression and propagation of heritable and non-heritable factors through regulatory networks. We find that the decisive factor in determining whether a gene will be influenced by a drug is the flow of heritable effects supplied to the gene through regulatory network.

  @article{noauthororeditor,
  abstract = {The blood gene expression signatures are used as biomarkers for immunological and non- immunological diseases. Therefore, it is important to understand the variation in blood gene expression patterns and the factors (heritable/non-heritable) that underlie this variation. In this paper, we study the relationship between drug effects on the one hand, and heritable and non-heritable factors influencing gene expression on the other. Understanding of this relationship can help select appropriate targets for drugs aimed at reverting disease phenotypes to healthy states. In order to estimate heritable and non-heritable effects on gene expression, we use Twin-ACE model on a gene expression dataset MuTHER, measured in blood samples from monozygotic and dizygotic twins. In order to associate gene expression with drug effects, we use CMap database. We show that, even though the expressions of most genes are driven by non-heritable factors, drugs are more likely to influence expression of genes, driven by heritable rather than non-heritable factors. We further study this finding in the context of a gene regulatory network. We investigate the relationship between the drug effects on gene expression and propagation of heritable and non-heritable factors through regulatory networks. We find that the decisive factor in determining whether a gene will be influenced by a drug is the flow of heritable effects supplied to the gene through regulatory network.},
  author = {Gao, Tianxiang and Brodin, Petter and Davis, MM and Jojic, Vladimir},
  journal = {Biocomputing},
  keywords = {Heritable},
  pages = {395-406},
  title = {Drug-induced mRNA signatures are enriched for the minority of genes that are highly heritable.},
  year = 2015
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Gao, Tianxiang
  %A Brodin, Petter
  %A Davis, MM
  %A Jojic, Vladimir
  %D 2015
  %J Biocomputing
  %P 395-406
  %R https://doi.org/10.1142/9789814644730_0038Cited
  %T Drug-induced mRNA signatures are enriched for the minority of genes that are highly heritable.
  %X The blood gene expression signatures are used as biomarkers for immunological and non- immunological diseases. Therefore, it is important to understand the variation in blood gene expression patterns and the factors (heritable/non-heritable) that underlie this variation. In this paper, we study the relationship between drug effects on the one hand, and heritable and non-heritable factors influencing gene expression on the other. Understanding of this relationship can help select appropriate targets for drugs aimed at reverting disease phenotypes to healthy states. In order to estimate heritable and non-heritable effects on gene expression, we use Twin-ACE model on a gene expression dataset MuTHER, measured in blood samples from monozygotic and dizygotic twins. In order to associate gene expression with drug effects, we use CMap database. We show that, even though the expressions of most genes are driven by non-heritable factors, drugs are more likely to influence expression of genes, driven by heritable rather than non-heritable factors. We further study this finding in the context of a gene regulatory network. We investigate the relationship between the drug effects on gene expression and propagation of heritable and non-heritable factors through regulatory networks. We find that the decisive factor in determining whether a gene will be influenced by a drug is the flow of heritable effects supplied to the gene through regulatory network.
  

• 1.

  Nakasone, H., Remberger, M., Tian, L., Brodin, P., Sahaf, B., Wu, F., Mattsson, J., Lowsky, R., Negrin, R., Miklos, D. B., and Meyer, E. (2015) Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy., Haematologica 100, 1477–1485.

  AbstractBibTeXEndNoteDOIBibSonomy

  Sex-mismatched hematopoietic cell transplantation is linked to increased graft-versus-host disease and mortality in myeloablative conditioning. Here we evaluated outcomes of 1,041 adult transplant recipients at two centers between 2006 and 2013 and investigated how the effect of sex-mismatching differed in myeloablative, reduced-intensity, and non-myeloablative total lymphoid irradiation with anti-thymocyte globulin conditioning. Among patients who underwent myeloablative conditioning, male recipients with female donors had increased chronic graft-versus-host disease (hazard ratio 1.83, P<0.01), increased non-relapse mortality (hazard ratio 1.84, P=0.022) and inferior overall survival (hazard ratio 1.59, P=0.018). In contrast, among patients who received reduced-intensity conditioning, male recipients with female donors had increased acute graft-versus-host disease (hazard ratio 1.96, P<0.01) but no difference in non-relapse mortality or overall survival. Among the patients who underwent total lymphoid irradiation with anti-thymocyte globulin, male recipients with female donors showed no increase in graft-versus-host disease or non-relapse mortality. Notably, only in the cohort receiving total lymphoid irradiation with anti-thymocyte globulin were male recipients with female donors significantly associated with reduced relapse (hazard ratio 0.64, P<0.01), and allo-antibody responses against H-Y antigens were predictive of reduced relapse. In the cohort given total lymphoid irradiation with anti-thymocyte globulin, the graft-versus-leukemia effect resulted in superior overall survival in recipients of sex-mismatched grafts (HR 0.69, P=0.037). In addition, only in the cohort treated with total lymphoid irradiation with anti-thymocyte globulin were female recipients with male donors associated with reduced relapse (hazard ratio 0.59, P<0.01) and superior survival (hazard ratio 0.61, P=0.014) compared with sex-matched pairs. We conclude that the risks and benefits of sex-mismatched transplants appear to differ according to conditioning strategy and this could affect donor selection.

  @article{noauthororeditor,
  abstract = {Sex-mismatched hematopoietic cell transplantation is linked to increased graft-versus-host disease and mortality in myeloablative conditioning. Here we evaluated outcomes of 1,041 adult transplant recipients at two centers between 2006 and 2013 and investigated how the effect of sex-mismatching differed in myeloablative, reduced-intensity, and non-myeloablative total lymphoid irradiation with anti-thymocyte globulin conditioning. Among patients who underwent myeloablative conditioning, male recipients with female donors had increased chronic graft-versus-host disease (hazard ratio 1.83, P<0.01), increased non-relapse mortality (hazard ratio 1.84, P=0.022) and inferior overall survival (hazard ratio 1.59, P=0.018). In contrast, among patients who received reduced-intensity conditioning, male recipients with female donors had increased acute graft-versus-host disease (hazard ratio 1.96, P<0.01) but no difference in non-relapse mortality or overall survival. Among the patients who underwent total lymphoid irradiation with anti-thymocyte globulin, male recipients with female donors showed no increase in graft-versus-host disease or non-relapse mortality. Notably, only in the cohort receiving total lymphoid irradiation with anti-thymocyte globulin were male recipients with female donors significantly associated with reduced relapse (hazard ratio 0.64, P<0.01), and allo-antibody responses against H-Y antigens were predictive of reduced relapse. In the cohort given total lymphoid irradiation with anti-thymocyte globulin, the graft-versus-leukemia effect resulted in superior overall survival in recipients of sex-mismatched grafts (HR 0.69, P=0.037). In addition, only in the cohort treated with total lymphoid irradiation with anti-thymocyte globulin were female recipients with male donors associated with reduced relapse (hazard ratio 0.59, P<0.01) and superior survival (hazard ratio 0.61, P=0.014) compared with sex-matched pairs. We conclude that the risks and benefits of sex-mismatched transplants appear to differ according to conditioning strategy and this could affect donor selection.},
  author = {Nakasone, Hideki and Remberger, Mats and Tian, Lu and Brodin, Petter and Sahaf, Bita and Wu, Fang and Mattsson, Jonas and Lowsky, Robert and Negrin, Robert and Miklos, David B and Meyer, Everett},
  journal = {Haematologica},
  keywords = {HSCT},
  month = {November},
  number = 11,
  pages = {1477-1485},
  title = {Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy.},
  volume = 100,
  year = 2015
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Nakasone, Hideki
  %A Remberger, Mats
  %A Tian, Lu
  %A Brodin, Petter
  %A Sahaf, Bita
  %A Wu, Fang
  %A Mattsson, Jonas
  %A Lowsky, Robert
  %A Negrin, Robert
  %A Miklos, David B
  %A Meyer, Everett
  %D 2015
  %J Haematologica
  %N 11
  %P 1477-1485
  %R 10.3324/haematol.2015.125294
  %T Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy.
  %V 100
  %X Sex-mismatched hematopoietic cell transplantation is linked to increased graft-versus-host disease and mortality in myeloablative conditioning. Here we evaluated outcomes of 1,041 adult transplant recipients at two centers between 2006 and 2013 and investigated how the effect of sex-mismatching differed in myeloablative, reduced-intensity, and non-myeloablative total lymphoid irradiation with anti-thymocyte globulin conditioning. Among patients who underwent myeloablative conditioning, male recipients with female donors had increased chronic graft-versus-host disease (hazard ratio 1.83, P<0.01), increased non-relapse mortality (hazard ratio 1.84, P=0.022) and inferior overall survival (hazard ratio 1.59, P=0.018). In contrast, among patients who received reduced-intensity conditioning, male recipients with female donors had increased acute graft-versus-host disease (hazard ratio 1.96, P<0.01) but no difference in non-relapse mortality or overall survival. Among the patients who underwent total lymphoid irradiation with anti-thymocyte globulin, male recipients with female donors showed no increase in graft-versus-host disease or non-relapse mortality. Notably, only in the cohort receiving total lymphoid irradiation with anti-thymocyte globulin were male recipients with female donors significantly associated with reduced relapse (hazard ratio 0.64, P<0.01), and allo-antibody responses against H-Y antigens were predictive of reduced relapse. In the cohort given total lymphoid irradiation with anti-thymocyte globulin, the graft-versus-leukemia effect resulted in superior overall survival in recipients of sex-mismatched grafts (HR 0.69, P=0.037). In addition, only in the cohort treated with total lymphoid irradiation with anti-thymocyte globulin were female recipients with male donors associated with reduced relapse (hazard ratio 0.59, P<0.01) and superior survival (hazard ratio 0.61, P=0.014) compared with sex-matched pairs. We conclude that the risks and benefits of sex-mismatched transplants appear to differ according to conditioning strategy and this could affect donor selection.
  

• 1.

  Shekhar, K., Brodin, P., Davis, M., and Chakraborty, A. K. (2014) Automatic Classification of Cellular Expression by Nonlinear Stochastic Embedding (ACCENSE)., Proceedings of the National Academy of Sciences of the United States of America 111, 202–207.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Shekhar, Karthik and Brodin, Petter and Davis, MM and Chakraborty, Arup K},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {ACCENSE},
  month = {January},
  number = 1,
  pages = {202-207},
  title = {Automatic Classification of Cellular Expression by Nonlinear Stochastic Embedding (ACCENSE).},
  volume = 111,
  year = 2014
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Shekhar, Karthik
  %A Brodin, Petter
  %A Davis, MM
  %A Chakraborty, Arup K
  %D 2014
  %J Proceedings of the National Academy of Sciences of the United States of America
  %N 1
  %P 202-207
  %R 10.1073/pnas.1321405111
  %T Automatic Classification of Cellular Expression by Nonlinear Stochastic Embedding (ACCENSE).
  %V 111
  

• 1.

  Sternberg-Simon, M., Brodin, P., Pickman, Y., Önfelt, B., Kärre, K., Malmberg, K.-J., Höglund, P., and Mehr, R. (2013) Natural Killer Cell Inhibitory Receptor Expression in Humans and Mice: A Closer Look, Frontiers in Immunology, Frontiers Media SA 4.

  URLBibTeXEndNoteDOIBibSonomy

  @article{Sternberg_Simon_2013,
  author = {Sternberg-Simon, Michal and Brodin, Petter and Pickman, Yishai and Önfelt, Björn and Kärre, Klas and Malmberg, Karl-Johan and Höglund, Petter and Mehr, Ramit},
  journal = {Frontiers in Immunology},
  keywords = {nk},
  publisher = {Frontiers Media SA},
  title = {Natural Killer Cell Inhibitory Receptor Expression in Humans and Mice: A Closer Look},
  volume = 4,
  year = 2013
  }
  

  %0 Journal Article
  %1 Sternberg_Simon_2013
  %A Sternberg-Simon, Michal
  %A Brodin, Petter
  %A Pickman, Yishai
  %A Önfelt, Björn
  %A Kärre, Klas
  %A Malmberg, Karl-Johan
  %A Höglund, Petter
  %A Mehr, Ramit
  %D 2013
  %I Frontiers Media SA
  %J Frontiers in Immunology
  %R 10.3389/fimmu.2013.00065
  %T Natural Killer Cell Inhibitory Receptor Expression in Humans and Mice: A Closer Look
  %U https://doi.org/10.3389%2Ffimmu.2013.00065
  %V 4
  

• 1.

  Brodin, P., Valentini, D., Uhlin, M., Mattsson, J., Zumla, A., and Maeurer, M. J. (2013) Systems level immune response analysis and personalized medicine., Expert Review of Clinical Immunology 9, 307–317.

  AbstractBibTeXEndNoteDOIBibSonomy

  The immune system is an anatomically structured, orchestrated interaction of different cell types that communicate via a large number of receptors recognizing both soluble and cellular ligands. Recent technological advances now allow large-scale measurements for better appreciation of this complexity. Despite these advances, only a few immunological parameters are routinely measured in clinical practice. The authors believe that these measurements are insufficient to describe the immune function of individual patients and thus cannot be used to evaluate immune-mediated diseases or response to therapy. Our current knowledge of immunology comes largely from work in murine model systems where the immune system has been characterized in great detail. This impressive volume of knowledge has proven to be difficult to translate into novel therapies in humans; one reason for this is the lack of large-scale immune monitoring allowing for systems-wide analysis of the human immune system. The authors propose a systems approach to immunology, where the focus is moved from analysis of individual cell types towards more integrated studies of the entire immune system. Exercising 'systems immunology' in preclinical research, during drug development and in patients undergoing therapies affecting the immune system, will enable us to improve clinical results through personalized medicine and help to define clinically relevant patterns of immune reactivity.

  @article{noauthororeditor,
  abstract = {The immune system is an anatomically structured, orchestrated interaction of different cell types that communicate via a large number of receptors recognizing both soluble and cellular ligands. Recent technological advances now allow large-scale measurements for better appreciation of this complexity. Despite these advances, only a few immunological parameters are routinely measured in clinical practice. The authors believe that these measurements are insufficient to describe the immune function of individual patients and thus cannot be used to evaluate immune-mediated diseases or response to therapy. Our current knowledge of immunology comes largely from work in murine model systems where the immune system has been characterized in great detail. This impressive volume of knowledge has proven to be difficult to translate into novel therapies in humans; one reason for this is the lack of large-scale immune monitoring allowing for systems-wide analysis of the human immune system. The authors propose a systems approach to immunology, where the focus is moved from analysis of individual cell types towards more integrated studies of the entire immune system. Exercising 'systems immunology' in preclinical research, during drug development and in patients undergoing therapies affecting the immune system, will enable us to improve clinical results through personalized medicine and help to define clinically relevant patterns of immune reactivity.},
  author = {Brodin, Petter and Valentini, Davide and Uhlin, Michael and Mattsson, Jonas and Zumla, Alimuddin and Maeurer, Markus J},
  journal = {Expert Review of Clinical Immunology},
  keywords = {Medicine Personalized},
  month = {April},
  number = 4,
  pages = {307-317},
  title = {Systems level immune response analysis and personalized medicine.},
  volume = 9,
  year = 2013
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Brodin, Petter
  %A Valentini, Davide
  %A Uhlin, Michael
  %A Mattsson, Jonas
  %A Zumla, Alimuddin
  %A Maeurer, Markus J
  %D 2013
  %J Expert Review of Clinical Immunology
  %N 4
  %P 307-317
  %R 10.1586/eci.13.9
  %T Systems level immune response analysis and personalized medicine.
  %V 9
  %X The immune system is an anatomically structured, orchestrated interaction of different cell types that communicate via a large number of receptors recognizing both soluble and cellular ligands. Recent technological advances now allow large-scale measurements for better appreciation of this complexity. Despite these advances, only a few immunological parameters are routinely measured in clinical practice. The authors believe that these measurements are insufficient to describe the immune function of individual patients and thus cannot be used to evaluate immune-mediated diseases or response to therapy. Our current knowledge of immunology comes largely from work in murine model systems where the immune system has been characterized in great detail. This impressive volume of knowledge has proven to be difficult to translate into novel therapies in humans; one reason for this is the lack of large-scale immune monitoring allowing for systems-wide analysis of the human immune system. The authors propose a systems approach to immunology, where the focus is moved from analysis of individual cell types towards more integrated studies of the entire immune system. Exercising 'systems immunology' in preclinical research, during drug development and in patients undergoing therapies affecting the immune system, will enable us to improve clinical results through personalized medicine and help to define clinically relevant patterns of immune reactivity.
  

• 1.

  Brodin, P., Lakshmikanth, T., Kärre, K., and Höglund, P. (2012) Skewing of the NK cell repertoire by MHC class I via quantitatively controlled enrichment and contraction of specific Ly49 subsets., The journal of immunology 188, 2218–2226.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Brodin, Petter and Lakshmikanth, Tadepally and Kärre, Klas and Höglund, Petter},
  journal = {The journal of immunology},
  keywords = {nk},
  month = {March},
  number = 5,
  pages = {2218-2226},
  title = {Skewing of the NK cell repertoire by MHC class I via quantitatively controlled enrichment and contraction of specific Ly49 subsets.},
  volume = 188,
  year = 2012
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Brodin, Petter
  %A Lakshmikanth, Tadepally
  %A Kärre, Klas
  %A Höglund, Petter
  %D 2012
  %J The journal of immunology
  %N 5
  %P 2218-2226
  %R 10.4049/jimmunol.1102801
  %T Skewing of the NK cell repertoire by MHC class I via quantitatively controlled enrichment and contraction of specific Ly49 subsets.
  %V 188
  

• 1.

  Brodin, P., Gilg, S., Lundell, L., and Mattsson, J. (2012) Major surgery in a neutropenic patient undergoing allogeneic stem cell transplantation for high risk myelofibrosis, International Journal of Hematology 96, 798–800.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Certain homeostatic functions are particularly important to the success of extensive surgery. For example metabolic homeostasis, inflammation and tissue repair, coagulation and immune defense against infection are all of great importance. In patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT), the ability to mount adequate inflammatory responses is severely impaired. Thrombocytopenia is common making coagulation inadequate for any kind of invasive procedure, let alone extensive surgery. For this reason, abdominal surgery in neutropenic patients is associated with very high mortality rates of between 50 and 70 % [1]. Here, we describe a patient with high-risk myelofibrosis who required extensive abdominal surgery during the aplastic phase only 7 days after ASCT due to severe abdominal hemorrhage. This patient's successful recovery shows that extensive surgery is possible even during the aplastic phase after ASCT. Interestingly, we also found that radical splenectomy 7 days after stem cell transplantation did not lead to any significant loss of infused stem cells.

  @article{Brodin2012,
  abstract = {Certain homeostatic functions are particularly important to the success of extensive surgery. For example metabolic homeostasis, inflammation and tissue repair, coagulation and immune defense against infection are all of great importance. In patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT), the ability to mount adequate inflammatory responses is severely impaired. Thrombocytopenia is common making coagulation inadequate for any kind of invasive procedure, let alone extensive surgery. For this reason, abdominal surgery in neutropenic patients is associated with very high mortality rates of between 50 and 70 % [1]. Here, we describe a patient with high-risk myelofibrosis who required extensive abdominal surgery during the aplastic phase only 7 days after ASCT due to severe abdominal hemorrhage. This patient's successful recovery shows that extensive surgery is possible even during the aplastic phase after ASCT. Interestingly, we also found that radical splenectomy 7 days after stem cell transplantation did not lead to any significant loss of infused stem cells.},
  author = {Brodin, Petter and Gilg, Stefan and Lundell, Lars and Mattsson, Jonas},
  journal = {International Journal of Hematology},
  keywords = {ASCT},
  month = {dec},
  number = 6,
  pages = {798--800},
  title = {Major surgery in a neutropenic patient undergoing allogeneic stem cell transplantation for high risk myelofibrosis},
  volume = 96,
  year = 2012
  }
  

  %0 Journal Article
  %1 Brodin2012
  %A Brodin, Petter
  %A Gilg, Stefan
  %A Lundell, Lars
  %A Mattsson, Jonas
  %D 2012
  %J International Journal of Hematology
  %N 6
  %P 798--800
  %R 10.1007/s12185-012-1178-7
  %T Major surgery in a neutropenic patient undergoing allogeneic stem cell transplantation for high risk myelofibrosis
  %U https://doi.org/10.1007/s12185-012-1178-7
  %V 96
  %X Certain homeostatic functions are particularly important to the success of extensive surgery. For example metabolic homeostasis, inflammation and tissue repair, coagulation and immune defense against infection are all of great importance. In patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT), the ability to mount adequate inflammatory responses is severely impaired. Thrombocytopenia is common making coagulation inadequate for any kind of invasive procedure, let alone extensive surgery. For this reason, abdominal surgery in neutropenic patients is associated with very high mortality rates of between 50 and 70 % [1]. Here, we describe a patient with high-risk myelofibrosis who required extensive abdominal surgery during the aplastic phase only 7 days after ASCT due to severe abdominal hemorrhage. This patient's successful recovery shows that extensive surgery is possible even during the aplastic phase after ASCT. Interestingly, we also found that radical splenectomy 7 days after stem cell transplantation did not lead to any significant loss of infused stem cells.
  

• 1.

  Lovén, J., Zinin, N., Wahlström, T., Müller, I., Brodin, P., Fredlund, E., Ribacke, U., Pivarcsi, A., Påhlman, S., and Henriksson, M. (2010) MYCN-regulated microRNAs repress estrogen receptor-alpha (ESR1) expression and neuronal differentiation in human neuroblastoma., Proceedings of the National Academy of Sciences of the United States of America 107, 1553–1558.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Lovén, Jakob and Zinin, Nikolay and Wahlström, Therese and Müller, Inga and Brodin, Petter and Fredlund, Erik and Ribacke, Ulf and Pivarcsi, Andor and Påhlman, Sven and Henriksson, Marie},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {microrna},
  month = {January},
  number = 4,
  pages = {1553-1558},
  title = {MYCN-regulated microRNAs repress estrogen receptor-alpha (ESR1) expression and neuronal differentiation in human neuroblastoma.},
  volume = 107,
  year = 2010
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Lovén, Jakob
  %A Zinin, Nikolay
  %A Wahlström, Therese
  %A Müller, Inga
  %A Brodin, Petter
  %A Fredlund, Erik
  %A Ribacke, Ulf
  %A Pivarcsi, Andor
  %A Påhlman, Sven
  %A Henriksson, Marie
  %D 2010
  %J Proceedings of the National Academy of Sciences of the United States of America
  %N 4
  %P 1553-1558
  %R 10.1073/pnas.0913517107
  %T MYCN-regulated microRNAs repress estrogen receptor-alpha (ESR1) expression and neuronal differentiation in human neuroblastoma.
  %V 107
  

• 1.

  Hoglund, P., and Brodin, P. (2010) Current perspectives of natural killer cell education by MHC class I molecules., Nature Reviews Immunology 10, 724–734.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Hoglund, Petter and Brodin, Petter},
  journal = {Nature Reviews Immunology},
  keywords = {nk},
  month = {October},
  number = 10,
  pages = {724-734},
  title = {Current perspectives of natural killer cell education by MHC class I molecules.},
  volume = 10,
  year = 2010
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Hoglund, Petter
  %A Brodin, Petter
  %D 2010
  %J Nature Reviews Immunology
  %N 10
  %P 724-734
  %R 10.1038/nri2835
  %T Current perspectives of natural killer cell education by MHC class I molecules.
  %V 10
  

• 1.

  Brodin, P., Lakshmikanth, T., Mehr, R., Johansson, M. H., Duru, A. D., Achour, A., Salmon-Divon, M., Kärre, K., Höglund, P., and Johansson, S. (2010) Natural Killer Cell Tolerance Persists Despite Significant Reduction of Self MHC Class I on Normal Target Cells in Mice, PLOS ONE, Public Library of Science 5, 1–12.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Background A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8+ T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any further effect on the degree of Ly49 downmodulation. Furthermore, a single MHC class I allele could downmodulate up to three Ly49 receptors on individual NK cells. Only when NK cells simultaneously expressed several Ly49 receptors and hemizygous MHC class I levels, a putative threshold for Ly49 downmodulation was reached. Conclusion Collectively, our findings suggest that in interactions between NK cells and normal untransformed cells, MHC class I molecules are in most cases expressed in excess compared to what is functionally needed to ensure self tolerance and to induce maximal Ly49 downmodulation. We speculate that the reason for this is to maintain a safety margin for otherwise normal, autologous cells over a range of MHC class I expression levels, in order to ensure robustness in NK cell tolerance.

  @article{10.1371/journal.pone.0013174,
  abstract = {Background A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8+ T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any further effect on the degree of Ly49 downmodulation. Furthermore, a single MHC class I allele could downmodulate up to three Ly49 receptors on individual NK cells. Only when NK cells simultaneously expressed several Ly49 receptors and hemizygous MHC class I levels, a putative threshold for Ly49 downmodulation was reached. Conclusion Collectively, our findings suggest that in interactions between NK cells and normal untransformed cells, MHC class I molecules are in most cases expressed in excess compared to what is functionally needed to ensure self tolerance and to induce maximal Ly49 downmodulation. We speculate that the reason for this is to maintain a safety margin for otherwise normal, autologous cells over a range of MHC class I expression levels, in order to ensure robustness in NK cell tolerance.},
  author = {Brodin, Petter and Lakshmikanth, Tadepally and Mehr, Ramit and Johansson, Maria H. and Duru, Adil Doganay and Achour, Adnane and Salmon-Divon, Mali and Kärre, Klas and Höglund, Petter and Johansson, Sofia},
  journal = {PLOS ONE},
  keywords = {nk},
  month = 10,
  number = 10,
  pages = {1-12},
  publisher = {Public Library of Science},
  title = {Natural Killer Cell Tolerance Persists Despite Significant Reduction of Self MHC Class I on Normal Target Cells in Mice},
  volume = 5,
  year = 2010
  }
  

  %0 Journal Article
  %1 10.1371/journal.pone.0013174
  %A Brodin, Petter
  %A Lakshmikanth, Tadepally
  %A Mehr, Ramit
  %A Johansson, Maria H.
  %A Duru, Adil Doganay
  %A Achour, Adnane
  %A Salmon-Divon, Mali
  %A Kärre, Klas
  %A Höglund, Petter
  %A Johansson, Sofia
  %D 2010
  %I Public Library of Science
  %J PLOS ONE
  %N 10
  %P 1-12
  %R 10.1371/journal.pone.0013174
  %T Natural Killer Cell Tolerance Persists Despite Significant Reduction of Self MHC Class I on Normal Target Cells in Mice
  %U https://doi.org/10.1371/journal.pone.0013174
  %V 5
  %X Background A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8+ T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any further effect on the degree of Ly49 downmodulation. Furthermore, a single MHC class I allele could downmodulate up to three Ly49 receptors on individual NK cells. Only when NK cells simultaneously expressed several Ly49 receptors and hemizygous MHC class I levels, a putative threshold for Ly49 downmodulation was reached. Conclusion Collectively, our findings suggest that in interactions between NK cells and normal untransformed cells, MHC class I molecules are in most cases expressed in excess compared to what is functionally needed to ensure self tolerance and to induce maximal Ly49 downmodulation. We speculate that the reason for this is to maintain a safety margin for otherwise normal, autologous cells over a range of MHC class I expression levels, in order to ensure robustness in NK cell tolerance.
  

• 1.

  Thams, S., Brodin, P., Plantman, S., Saxelin, R., Kärre, K., and Cullheim, S. (2009) Classical major histocompatibility complex class I molecules in motoneurons: new actors at the neuromuscular junction., The journal of neuroscience 29, 13503–13515.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Thams, Sebastian and Brodin, Petter and Plantman, Stefan and Saxelin, Robert and Kärre, Klas and Cullheim, Staffan},
  journal = {The journal of neuroscience},
  keywords = {MHC-I},
  month = {October},
  number = 43,
  pages = {13503-13515},
  title = {Classical major histocompatibility complex class I molecules in motoneurons: new actors at the neuromuscular junction.},
  volume = 29,
  year = 2009
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Thams, Sebastian
  %A Brodin, Petter
  %A Plantman, Stefan
  %A Saxelin, Robert
  %A Kärre, Klas
  %A Cullheim, Staffan
  %D 2009
  %J The journal of neuroscience
  %N 43
  %P 13503-13515
  %R 10.1523/JNEUROSCI.0981-09.2009
  %T Classical major histocompatibility complex class I molecules in motoneurons: new actors at the neuromuscular junction.
  %V 29
  

• 1.

  Cheng, M., Charoudeh, H. N., Brodin, P., Tang, Y., Lakshmikanth, T., Höglund, P., Jacobsen, S. E. W., and Sitnicka, E. (2009) Distinct and overlapping patterns of cytokine regulation of thymic and bone marrow-derived NK cell development., The journal of immunology 182, 1460–1468.

  AbstractBibTeXEndNoteDOIBibSonomy

  Although bone marrow (BM) represents the main site for postnatal NK cell development, recently a distinct thymic-dependent NK cell pathway was identified. These studies were designed to investigate the role of cytokines in regulation of thymic NK cells and to compare with established regulatory pathways of BM-dependent NK cell compartment. The common cytokine receptor gamma-chain (Il2rg) essential for IL-15-induced signaling, and FMS-like tyrosine kinase 3 (FLT3) receptor ligand (Flt3l) were previously identified as important regulatory pathways of the BM NK cell compartment based on lack of function studies in mice, however their complementary action remains unknown. By investigating mice double-deficient in Il2rg and Flt3l (Flt3l(-/-) Il2rg(-/-)), we demonstrate that FLT3L is important for IL2Rg-independent maintenance of both immature BM as well as peripheral NK cells. In contrast to IL-7, which is dispensable for BM but important for thymic NK cells, IL-15 has a direct and important role in both thymic and BM NK cell compartments. Although thymic NK cells were not affected in Flt3l(-/-) mice, Flt3l(-/-)Il2rg(-/-) mice lacked detectable thymic NK cells, suggesting that FLT3L is also important for IL-2Rg-independent maintenance of thymic NK cells. Thus, IL-2Rg cytokines and FLT3L play complementary roles and are indispensable for homeostasis of both BM and thymic dependent NK cell development, suggesting that the cytokine pathways crucial for these two distinct NK cell pathways are largely overlapping.

  @article{noauthororeditor,
  abstract = {Although bone marrow (BM) represents the main site for postnatal NK cell development, recently a distinct thymic-dependent NK cell pathway was identified. These studies were designed to investigate the role of cytokines in regulation of thymic NK cells and to compare with established regulatory pathways of BM-dependent NK cell compartment. The common cytokine receptor gamma-chain (Il2rg) essential for IL-15-induced signaling, and FMS-like tyrosine kinase 3 (FLT3) receptor ligand (Flt3l) were previously identified as important regulatory pathways of the BM NK cell compartment based on lack of function studies in mice, however their complementary action remains unknown. By investigating mice double-deficient in Il2rg and Flt3l (Flt3l(-/-) Il2rg(-/-)), we demonstrate that FLT3L is important for IL2Rg-independent maintenance of both immature BM as well as peripheral NK cells. In contrast to IL-7, which is dispensable for BM but important for thymic NK cells, IL-15 has a direct and important role in both thymic and BM NK cell compartments. Although thymic NK cells were not affected in Flt3l(-/-) mice, Flt3l(-/-)Il2rg(-/-) mice lacked detectable thymic NK cells, suggesting that FLT3L is also important for IL-2Rg-independent maintenance of thymic NK cells. Thus, IL-2Rg cytokines and FLT3L play complementary roles and are indispensable for homeostasis of both BM and thymic dependent NK cell development, suggesting that the cytokine pathways crucial for these two distinct NK cell pathways are largely overlapping.},
  author = {Cheng, Min and Charoudeh, Hojjatollah Nozad and Brodin, Petter and Tang, Yanjuan and Lakshmikanth, Tadepally and Höglund, Petter and Jacobsen, Sten Eirik W and Sitnicka, Ewa},
  journal = {The journal of immunology},
  keywords = {nk},
  month = {February},
  number = 3,
  pages = {1460-1468},
  title = {Distinct and overlapping patterns of cytokine regulation of thymic and bone marrow-derived NK cell development.},
  volume = 182,
  year = 2009
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Cheng, Min
  %A Charoudeh, Hojjatollah Nozad
  %A Brodin, Petter
  %A Tang, Yanjuan
  %A Lakshmikanth, Tadepally
  %A Höglund, Petter
  %A Jacobsen, Sten Eirik W
  %A Sitnicka, Ewa
  %D 2009
  %J The journal of immunology
  %N 3
  %P 1460-1468
  %R 10.4049/jimmunol.182.3.1460
  %T Distinct and overlapping patterns of cytokine regulation of thymic and bone marrow-derived NK cell development.
  %V 182
  %X Although bone marrow (BM) represents the main site for postnatal NK cell development, recently a distinct thymic-dependent NK cell pathway was identified. These studies were designed to investigate the role of cytokines in regulation of thymic NK cells and to compare with established regulatory pathways of BM-dependent NK cell compartment. The common cytokine receptor gamma-chain (Il2rg) essential for IL-15-induced signaling, and FMS-like tyrosine kinase 3 (FLT3) receptor ligand (Flt3l) were previously identified as important regulatory pathways of the BM NK cell compartment based on lack of function studies in mice, however their complementary action remains unknown. By investigating mice double-deficient in Il2rg and Flt3l (Flt3l(-/-) Il2rg(-/-)), we demonstrate that FLT3L is important for IL2Rg-independent maintenance of both immature BM as well as peripheral NK cells. In contrast to IL-7, which is dispensable for BM but important for thymic NK cells, IL-15 has a direct and important role in both thymic and BM NK cell compartments. Although thymic NK cells were not affected in Flt3l(-/-) mice, Flt3l(-/-)Il2rg(-/-) mice lacked detectable thymic NK cells, suggesting that FLT3L is also important for IL-2Rg-independent maintenance of thymic NK cells. Thus, IL-2Rg cytokines and FLT3L play complementary roles and are indispensable for homeostasis of both BM and thymic dependent NK cell development, suggesting that the cytokine pathways crucial for these two distinct NK cell pathways are largely overlapping.
  

• 1.

  Johansson, S., Salmon-Divon, M., Johansson, M. H., Pickman, Y., Brodin, P., Kärre, K., Mehr, R., and Höglund, P. (2009) Probing Natural Killer Cell Education by Ly49 Receptor Expression Analysis and Computational Modelling in Single MHC Class I Mice, PLOS ONE, Public Library of Science 4, 1–10.

  AbstractURLBibTeXEndNoteDOIBibSonomy

  Murine natural killer (NK) cells express inhibitory Ly49 receptors for MHC class I molecules, which allows for “missing self” recognition of cells that downregulate MHC class I expression. During murine NK cell development, host MHC class I molecules impose an “educating impact” on the NK cell pool. As a result, mice with different MHC class I expression display different frequency distributions of Ly49 receptor combinations on NK cells. Two models have been put forward to explain this impact. The two-step selection model proposes a stochastic Ly49 receptor expression followed by selection for NK cells expressing appropriate receptor combinations. The sequential model, on the other hand, proposes that each NK cell sequentially expresses Ly49 receptors until an interaction of sufficient magnitude with self-class I MHC is reached for the NK cell to mature. With the aim to clarify which one of these models is most likely to reflect the actual biological process, we simulated the two educational schemes by mathematical modelling, and fitted the results to Ly49 expression patterns, which were analyzed in mice expressing single MHC class I molecules. Our results favour the two-step selection model over the sequential model. Furthermore, the MHC class I environment favoured maturation of NK cells expressing one or a few self receptors, suggesting a possible step of positive selection in NK cell education. Based on the predicted Ly49 binding preferences revealed by the model, we also propose, that Ly49 receptors are more promiscuous than previously thought in their interactions with MHC class I molecules, which was supported by functional studies of NK cell subsets expressing individual Ly49 receptors.

  @article{10.1371/journal.pone.0006046,
  abstract = {Murine natural killer (NK) cells express inhibitory Ly49 receptors for MHC class I molecules, which allows for “missing self” recognition of cells that downregulate MHC class I expression. During murine NK cell development, host MHC class I molecules impose an “educating impact” on the NK cell pool. As a result, mice with different MHC class I expression display different frequency distributions of Ly49 receptor combinations on NK cells. Two models have been put forward to explain this impact. The two-step selection model proposes a stochastic Ly49 receptor expression followed by selection for NK cells expressing appropriate receptor combinations. The sequential model, on the other hand, proposes that each NK cell sequentially expresses Ly49 receptors until an interaction of sufficient magnitude with self-class I MHC is reached for the NK cell to mature. With the aim to clarify which one of these models is most likely to reflect the actual biological process, we simulated the two educational schemes by mathematical modelling, and fitted the results to Ly49 expression patterns, which were analyzed in mice expressing single MHC class I molecules. Our results favour the two-step selection model over the sequential model. Furthermore, the MHC class I environment favoured maturation of NK cells expressing one or a few self receptors, suggesting a possible step of positive selection in NK cell education. Based on the predicted Ly49 binding preferences revealed by the model, we also propose, that Ly49 receptors are more promiscuous than previously thought in their interactions with MHC class I molecules, which was supported by functional studies of NK cell subsets expressing individual Ly49 receptors.},
  author = {Johansson, Sofia and Salmon-Divon, Mali and Johansson, Maria H. and Pickman, Yishai and Brodin, Petter and Kärre, Klas and Mehr, Ramit and Höglund, Petter},
  journal = {PLOS ONE},
  keywords = {nk},
  month = {06},
  number = 6,
  pages = {1-10},
  publisher = {Public Library of Science},
  title = {Probing Natural Killer Cell Education by Ly49 Receptor Expression Analysis and Computational Modelling in Single MHC Class I Mice},
  volume = 4,
  year = 2009
  }
  

  %0 Journal Article
  %1 10.1371/journal.pone.0006046
  %A Johansson, Sofia
  %A Salmon-Divon, Mali
  %A Johansson, Maria H.
  %A Pickman, Yishai
  %A Brodin, Petter
  %A Kärre, Klas
  %A Mehr, Ramit
  %A Höglund, Petter
  %D 2009
  %I Public Library of Science
  %J PLOS ONE
  %N 6
  %P 1-10
  %R 10.1371/journal.pone.0006046
  %T Probing Natural Killer Cell Education by Ly49 Receptor Expression Analysis and Computational Modelling in Single MHC Class I Mice
  %U https://doi.org/10.1371/journal.pone.0006046
  %V 4
  %X Murine natural killer (NK) cells express inhibitory Ly49 receptors for MHC class I molecules, which allows for “missing self” recognition of cells that downregulate MHC class I expression. During murine NK cell development, host MHC class I molecules impose an “educating impact” on the NK cell pool. As a result, mice with different MHC class I expression display different frequency distributions of Ly49 receptor combinations on NK cells. Two models have been put forward to explain this impact. The two-step selection model proposes a stochastic Ly49 receptor expression followed by selection for NK cells expressing appropriate receptor combinations. The sequential model, on the other hand, proposes that each NK cell sequentially expresses Ly49 receptors until an interaction of sufficient magnitude with self-class I MHC is reached for the NK cell to mature. With the aim to clarify which one of these models is most likely to reflect the actual biological process, we simulated the two educational schemes by mathematical modelling, and fitted the results to Ly49 expression patterns, which were analyzed in mice expressing single MHC class I molecules. Our results favour the two-step selection model over the sequential model. Furthermore, the MHC class I environment favoured maturation of NK cells expressing one or a few self receptors, suggesting a possible step of positive selection in NK cell education. Based on the predicted Ly49 binding preferences revealed by the model, we also propose, that Ly49 receptors are more promiscuous than previously thought in their interactions with MHC class I molecules, which was supported by functional studies of NK cell subsets expressing individual Ly49 receptors.
  

• 1.

  Vahlne, G., Becker, S., Brodin, P., and Johansson, M. (2008) IFN-gamma production and degranulation are differentially regulated in response to stimulation in murine natural killer cells., Scandinavian journal of immunology 67, 1–11.

  BibTeXEndNoteDOIBibSonomy

  @article{noauthororeditor,
  author = {Vahlne, Gustaf and Becker, Stefan and Brodin, Petter and Johansson, MH},
  journal = {Scandinavian journal of immunology},
  keywords = {nk},
  month = {January},
  number = 1,
  pages = {1-11},
  title = {IFN-gamma production and degranulation are differentially regulated in response to stimulation in murine natural killer cells.},
  volume = 67,
  year = 2008
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Vahlne, Gustaf
  %A Becker, Stefan
  %A Brodin, Petter
  %A Johansson, MH
  %D 2008
  %J Scandinavian journal of immunology
  %N 1
  %P 1-11
  %R 10.1111/j.1365-3083.2007.02026.x
  %T IFN-gamma production and degranulation are differentially regulated in response to stimulation in murine natural killer cells.
  %V 67
  

• 1.

  Persson, C. M., Assarsson, E., Vahlne, G., Brodin, P., and Chambers, B. (2008) Critical role of Qa1b in the protection of mature dendritic cells from NK cell-mediated killing, Scandinavian journal of immunology 67, 30–36.

  AbstractBibTeXEndNoteDOIBibSonomy

  Molecular interactions in natural killer (NK) cell-mediated killing of dendritic cells (DC) have under recent years come under scrutiny. Upon stimulation with IFN-gamma or lipopolysaccharide, DC become relatively resistant to NK cell-mediated lysis. In the present study, we investigated the role of Qa1(b) on DC and its receptor NKG2A on NK cells in the protection of mature DC from NK cells. We demonstrate that while both NKG2A+ and NKG2A- NK cells can efficiently lyse unstimulated DC, NKG2A+ NK cells but not NKG2A- NK cells are largely impaired in their ability to lyse mature DC. Similarly, mature DC from mice expressing H-2D(b), whose leader peptide sequence binds and stabilizes Qa1(b), were resistant to NK cell-mediated killing, suggesting that stable Qa1(b) expression contributes to the protection of mature DC. This finding was further validated by the demonstration that addition of the Qdm leader peptide could protect TAP1-/- DC from NK cell-mediated lysis both in vitro and in vivo. The present data suggest that stable expression of Qa1 on the surface of mature DC contributes to the protection of DC from NK cell-mediated lysis.

  @article{noauthororeditor,
  abstract = {Molecular interactions in natural killer (NK) cell-mediated killing of dendritic cells (DC) have under recent years come under scrutiny. Upon stimulation with IFN-gamma or lipopolysaccharide, DC become relatively resistant to NK cell-mediated lysis. In the present study, we investigated the role of Qa1(b) on DC and its receptor NKG2A on NK cells in the protection of mature DC from NK cells. We demonstrate that while both NKG2A+ and NKG2A- NK cells can efficiently lyse unstimulated DC, NKG2A+ NK cells but not NKG2A- NK cells are largely impaired in their ability to lyse mature DC. Similarly, mature DC from mice expressing H-2D(b), whose leader peptide sequence binds and stabilizes Qa1(b), were resistant to NK cell-mediated killing, suggesting that stable Qa1(b) expression contributes to the protection of mature DC. This finding was further validated by the demonstration that addition of the Qdm leader peptide could protect TAP1-/- DC from NK cell-mediated lysis both in vitro and in vivo. The present data suggest that stable expression of Qa1 on the surface of mature DC contributes to the protection of DC from NK cell-mediated lysis.},
  author = {Persson, Catrine M and Assarsson, Erika and Vahlne, Gustaf and Brodin, Petter and Chambers, BJ},
  journal = {Scandinavian journal of immunology},
  keywords = {nk},
  month = {January},
  number = 1,
  pages = {30-36},
  title = {Critical role of Qa1b in the protection of mature dendritic cells from NK cell-mediated killing},
  volume = 67,
  year = 2008
  }
  

  %0 Journal Article
  %1 noauthororeditor
  %A Persson, Catrine M
  %A Assarsson, Erika
  %A Vahlne, Gustaf
  %A Brodin, Petter
  %A Chambers, BJ
  %D 2008
  %J Scandinavian journal of immunology
  %N 1
  %P 30-36
  %R 10.1111/j.1365-3083.2007.02034.x
  %T Critical role of Qa1b in the protection of mature dendritic cells from NK cell-mediated killing
  %V 67
  %X Molecular interactions in natural killer (NK) cell-mediated killing of dendritic cells (DC) have under recent years come under scrutiny. Upon stimulation with IFN-gamma or lipopolysaccharide, DC become relatively resistant to NK cell-mediated lysis. In the present study, we investigated the role of Qa1(b) on DC and its receptor NKG2A on NK cells in the protection of mature DC from NK cells. We demonstrate that while both NKG2A+ and NKG2A- NK cells can efficiently lyse unstimulated DC, NKG2A+ NK cells but not NKG2A- NK cells are largely impaired in their ability to lyse mature DC. Similarly, mature DC from mice expressing H-2D(b), whose leader peptide sequence binds and stabilizes Qa1(b), were resistant to NK cell-mediated killing, suggesting that stable Qa1(b) expression contributes to the protection of mature DC. This finding was further validated by the demonstration that addition of the Qdm leader peptide could protect TAP1-/- DC from NK cell-mediated lysis both in vitro and in vivo. The present data suggest that stable expression of Qa1 on the surface of mature DC contributes to the protection of DC from NK cell-mediated lysis.