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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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Autores principales: Ronit, Andreas, Jørgensen, Sofie E., Roed, Casper, Eriksson, Robert, Iepsen, Ulrik W., Plovsing, Ronni R., Storgaard, Merete, Gustafsson, Finn, Hansen, Ann-Brit E., Mogensen, Trine H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439578/
https://www.ncbi.nlm.nih.gov/pubmed/34531865
http://dx.doi.org/10.3389/fimmu.2021.718744
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author Ronit, Andreas
Jørgensen, Sofie E.
Roed, Casper
Eriksson, Robert
Iepsen, Ulrik W.
Plovsing, Ronni R.
Storgaard, Merete
Gustafsson, Finn
Hansen, Ann-Brit E.
Mogensen, Trine H.
author_facet Ronit, Andreas
Jørgensen, Sofie E.
Roed, Casper
Eriksson, Robert
Iepsen, Ulrik W.
Plovsing, Ronni R.
Storgaard, Merete
Gustafsson, Finn
Hansen, Ann-Brit E.
Mogensen, Trine H.
author_sort Ronit, Andreas
collection PubMed
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.
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spelling pubmed-84395782021-09-15 Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome Ronit, Andreas Jørgensen, Sofie E. Roed, Casper Eriksson, Robert Iepsen, Ulrik W. Plovsing, Ronni R. Storgaard, Merete Gustafsson, Finn Hansen, Ann-Brit E. Mogensen, Trine H. Front Immunol Immunology 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. Frontiers Media S.A. 2021-08-31 /pmc/articles/PMC8439578/ /pubmed/34531865 http://dx.doi.org/10.3389/fimmu.2021.718744 Text en Copyright © 2021 Ronit, Jørgensen, Roed, Eriksson, Iepsen, Plovsing, Storgaard, Gustafsson, Hansen and Mogensen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ronit, Andreas
Jørgensen, Sofie E.
Roed, Casper
Eriksson, Robert
Iepsen, Ulrik W.
Plovsing, Ronni R.
Storgaard, Merete
Gustafsson, Finn
Hansen, Ann-Brit E.
Mogensen, Trine H.
Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome
title 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_short 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
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439578/
https://www.ncbi.nlm.nih.gov/pubmed/34531865
http://dx.doi.org/10.3389/fimmu.2021.718744
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