BACKGROUND: Multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after the original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia, and activation of T cells with elevated IFN-γ. Observing the production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II, and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19. RESULTS: We documented a significant elevation of IFN-γ, but not IFN-α and IFN-λ in MIS-C patients. BAFF was elevated in MIS-C patient sera and accompanied by decreased BAFFR expression on all B cell subtypes. The proportion of plasmablasts was significantly lower in patients compared to healthy post-COVID children. We noted the pre-IVIG presence of ENA Ro60 autoantibodies in 4/35 tested MIS-C patients. CONCLUSIONS: Our work shows the involvement of humoral immunity in MIS-C and hints at parallels with the pathophysiology of SLE, with autoreactive B cells driven towards autoantibody production by elevated BAFF.

Department of Immunology 2nd Faculty of Medicine Charles University and University Hospital in Motol 5 Uvalu 84 150 06 Prague Czech Republic

Department of Paediatrics 1st Faculty of Medicine Charles University and Thomayer University Hospital Prague Czech Republic

Department of Paediatrics 2nd Faculty of Medicine Charles University and University Hospital in Motol Prague Czech Republic

Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Paediatrics PICU Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Pediatric Hematology CLIP Childhood Leukaemia Investigation Prague 2nd Faculty of Medicine Charles University and University Hospital in Motol Prague Czech Republic

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences IOCB Gilead Research Center Prague Czech Republic

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