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Diverse functional autoantibodies in patients with COVID-19 #MMPMID34010947
Wang EY; Mao T; Klein J; Dai Y; Huck JD; Jaycox JR; Liu F; Zhou T; Israelow B; Wong P; Coppi A; Lucas C; Silva J; Oh JE; Song E; Perotti ES; Zheng NS; Fischer S; Campbell M; Fournier JB; Wyllie AL; Vogels CBF; Ott IM; Kalinich CC; Petrone ME; Watkins AE; Dela Cruz C; Farhadian SF; Schulz WL; Ma S; Grubaugh ND; Ko AI; Iwasaki A; Ring AM
Nature 2021[Jul]; 595 (7866): 283-288 PMID34010947show ga
COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses(1-6). Although pathological innate immune activation is well-documented in severe disease(1), the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling(7) to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome). We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.
Nature 2021 ; 595 (7866): 283-288
