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Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome

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@article{1ae347b18bbc41a2b635aa5ee720cfa4,
title = "Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome",
abstract = "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.",
keywords = "Adult, Autoantibodies/blood, COVID-19/pathology, Chemokine CXCL10/biosynthesis, Comorbidity, Cytokines/blood, Exome/genetics, Female, Humans, Interferon-alpha/biosynthesis, Interferons/biosynthesis, Leukocytes, Mononuclear/immunology, Male, Middle Aged, SARS-CoV-2/immunology, Systemic Inflammatory Response Syndrome/pathology, Whole Exome Sequencing, Young Adult, interferon, whole exome sequencing, SARS-CoV-2, coronavirus disease 2019, multisystem inflammatory syndrome",
author = "Andreas Ronit and J{\o}rgensen, {Sofie E} and Casper Roed and Robert Eriksson and Iepsen, {Ulrik W} and Plovsing, {Ronni R} and Merete Storgaard and Finn Gustafsson and Hansen, {Ann-Brit E} and Mogensen, {Trine H}",
note = "Copyright {\textcopyright} 2021 Ronit, J{\o}rgensen, Roed, Eriksson, Iepsen, Plovsing, Storgaard, Gustafsson, Hansen and Mogensen.",
year = "2021",
month = aug,
day = "31",
doi = "10.3389/fimmu.2021.718744",
language = "English",
volume = "12",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome

AU - Ronit, Andreas

AU - Jørgensen, Sofie E

AU - Roed, Casper

AU - Eriksson, Robert

AU - Iepsen, Ulrik W

AU - Plovsing, Ronni R

AU - Storgaard, Merete

AU - Gustafsson, Finn

AU - Hansen, Ann-Brit E

AU - Mogensen, Trine H

N1 - Copyright © 2021 Ronit, Jørgensen, Roed, Eriksson, Iepsen, Plovsing, Storgaard, Gustafsson, Hansen and Mogensen.

PY - 2021/8/31

Y1 - 2021/8/31

N2 - 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.

AB - 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.

KW - Adult

KW - Autoantibodies/blood

KW - COVID-19/pathology

KW - Chemokine CXCL10/biosynthesis

KW - Comorbidity

KW - Cytokines/blood

KW - Exome/genetics

KW - Female

KW - Humans

KW - Interferon-alpha/biosynthesis

KW - Interferons/biosynthesis

KW - Leukocytes, Mononuclear/immunology

KW - Male

KW - Middle Aged

KW - SARS-CoV-2/immunology

KW - Systemic Inflammatory Response Syndrome/pathology

KW - Whole Exome Sequencing

KW - Young Adult

KW - interferon

KW - whole exome sequencing

KW - SARS-CoV-2

KW - coronavirus disease 2019

KW - multisystem inflammatory syndrome

UR - http://www.scopus.com/inward/record.url?scp=85115034401&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2021.718744

DO - 10.3389/fimmu.2021.718744

M3 - Journal article

C2 - 34531865

VL - 12

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 718744

ER -

ID: 67900496