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

• DOI: 10.3389/fimmu.2021.718744
• Publication Date: 2021-09-03T22:24:23Z
• Authors: Andreas Ronit; Sofie E. Jørgensen; Casper Roed; Robert Eriksson; Ulrik W. Iepsen; Ronni R. Plovsing; Merete Storgaard; Finn Gustafsson; Ann-Brit E. Hansen; Trine H. Mogensen
• Keywords: Proinflammatory cytokine; Pathogenesis

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, underlying pathogenesis unclear. We aimed to provide novel immunological genetic descriptions MIS-A patients. Cytokine responses (IL-6, IL-1β, TNFα, CXCL10, type I, II III interferons) following SARS-CoV-2 infection peripheral blood mononuclear cells in vitro were analyzed as well antibodies against IFNα IFNω (by ELISA) patients healthy controls. performed whole exome sequencing (WES) patient DNA. A total five (ages 19, 23, 33, 38, 50 years) included. The shared characteristic features, although organ involvement time course disease varied slightly. PBMCs revealed impaired I interferon reduced CXCL10 expression, whereas production proinflammatory cytokines less affected, compared Presence autoantibodies was not detected. Whole analysis DNA 12 potentially disease-causing variants genes related autophagy, classical Kawasaki disease, restriction factors immune responses. In conclusion, we observed an interferons response detected several gene contributing MIS-A.