Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome
COVID-19 associated multisystem inflammatory syndrome (MIS) is a rare condition mostly affecting children but also adults (MIS-A). Although severe systemic inflammation and multiorgan dysfunction are hallmarks of the syndrome, the underlying pathogenesis is unclear. We aimed to provide novel immunol...
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doaj-5ef054c53aeb4ca680c00a1cf8daeee02021-09-03T22:21:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.718744718744Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory SyndromeAndreas Ronit0Sofie E. Jørgensen1Sofie E. Jørgensen2Casper Roed3Robert Eriksson4Robert Eriksson5Ulrik W. Iepsen6Ronni R. Plovsing7Ronni R. Plovsing8Merete Storgaard9Finn Gustafsson10Finn Gustafsson11Ann-Brit E. Hansen12Trine H. Mogensen13Trine H. Mogensen14Department of Infectious Diseases 144, Hvidovre Hospital, University of Copenhagen, Hvidovre, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkDepartment of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, DenmarkDepartment of Anaesthesiology and Intensive Care, Hvidovre Hospital, University of Copenhagen, Hvidovre, DenmarkDepartment of Anaesthesiology and Intensive Care, Hvidovre Hospital, University of Copenhagen, Hvidovre, DenmarkDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkDepartment of Cardiology and Clinical Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of Infectious Diseases 144, Hvidovre Hospital, University of Copenhagen, Hvidovre, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkCOVID-19 associated multisystem inflammatory syndrome (MIS) is a rare condition mostly affecting children but also adults (MIS-A). Although severe systemic inflammation and multiorgan dysfunction are hallmarks of the syndrome, the underlying pathogenesis is unclear. We aimed to provide novel immunological and genetic descriptions of MIS-A patients. Cytokine responses (IL-6, IL-1β, TNFα, CXCL10, type I, II and III interferons) following SARS-CoV-2 infection of peripheral blood mononuclear cells in vitro were analyzed as well as antibodies against IFNα and IFNω (by ELISA) in patients and healthy controls. We also performed whole exome sequencing (WES) of patient DNA. A total of five patients (ages 19, 23, 33, 38, 50 years) were included. The patients shared characteristic features, although organ involvement and the time course of disease varied slightly. SARS-CoV-2 in vitro infection of patient PBMCs revealed impaired type I and III interferon responses and reduced CXCL10 expression, whereas production of proinflammatory cytokines were less affected, compared to healthy controls. Presence of interferon autoantibodies was not detected. Whole exome sequencing analysis of patient DNA revealed 12 rare potentially disease-causing variants in genes related to autophagy, classical Kawasaki disease, restriction factors and immune responses. In conclusion, we observed an impaired production of type I and III interferons in response to SARS-CoV-2 infection and detected several rare potentially disease-causing gene variants potentially contributing to MIS-A.https://www.frontiersin.org/articles/10.3389/fimmu.2021.718744/fullcoronavirus disease 2019multisystem inflammatory syndromeSARS-CoV-2whole exome sequencinginterferon |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andreas Ronit Sofie E. Jørgensen Sofie E. Jørgensen Casper Roed Robert Eriksson Robert Eriksson Ulrik W. Iepsen Ronni R. Plovsing Ronni R. Plovsing Merete Storgaard Finn Gustafsson Finn Gustafsson Ann-Brit E. Hansen Trine H. Mogensen Trine H. Mogensen |
spellingShingle |
Andreas Ronit Sofie E. Jørgensen Sofie E. Jørgensen Casper Roed Robert Eriksson Robert Eriksson Ulrik W. Iepsen Ronni R. Plovsing Ronni R. Plovsing Merete Storgaard Finn Gustafsson Finn Gustafsson Ann-Brit E. Hansen Trine H. Mogensen Trine H. Mogensen Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome Frontiers in Immunology coronavirus disease 2019 multisystem inflammatory syndrome SARS-CoV-2 whole exome sequencing interferon |
author_facet |
Andreas Ronit Sofie E. Jørgensen Sofie E. Jørgensen Casper Roed Robert Eriksson Robert Eriksson Ulrik W. Iepsen Ronni R. Plovsing Ronni R. Plovsing Merete Storgaard Finn Gustafsson Finn Gustafsson Ann-Brit E. Hansen Trine H. Mogensen Trine H. Mogensen |
author_sort |
Andreas Ronit |
title |
Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome |
title_short |
Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome |
title_full |
Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome |
title_fullStr |
Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome |
title_full_unstemmed |
Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome |
title_sort |
host genetics and antiviral immune responses in adult patients with multisystem inflammatory syndrome |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-08-01 |
description |
COVID-19 associated multisystem inflammatory syndrome (MIS) is a rare condition mostly affecting children but also adults (MIS-A). Although severe systemic inflammation and multiorgan dysfunction are hallmarks of the syndrome, the underlying pathogenesis is unclear. We aimed to provide novel immunological and genetic descriptions of MIS-A patients. Cytokine responses (IL-6, IL-1β, TNFα, CXCL10, type I, II and III interferons) following SARS-CoV-2 infection of peripheral blood mononuclear cells in vitro were analyzed as well as antibodies against IFNα and IFNω (by ELISA) in patients and healthy controls. We also performed whole exome sequencing (WES) of patient DNA. A total of five patients (ages 19, 23, 33, 38, 50 years) were included. The patients shared characteristic features, although organ involvement and the time course of disease varied slightly. SARS-CoV-2 in vitro infection of patient PBMCs revealed impaired type I and III interferon responses and reduced CXCL10 expression, whereas production of proinflammatory cytokines were less affected, compared to healthy controls. Presence of interferon autoantibodies was not detected. Whole exome sequencing analysis of patient DNA revealed 12 rare potentially disease-causing variants in genes related to autophagy, classical Kawasaki disease, restriction factors and immune responses. In conclusion, we observed an impaired production of type I and III interferons in response to SARS-CoV-2 infection and detected several rare potentially disease-causing gene variants potentially contributing to MIS-A. |
topic |
coronavirus disease 2019 multisystem inflammatory syndrome SARS-CoV-2 whole exome sequencing interferon |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.718744/full |
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