Diverse functional autoantibodies in patients with COVID-19

Autor: Mary E. Petrone, Carolina Lucas, Shelli F. Farhadian, Isabel M. Ott, Emily S. Perotti, Wade L. Schulz, Charles S. Dela Cruz, Chantal B.F. Vogels, Ji Eun Oh, Neil S Zheng, Anne L. Wyllie, Jillian R. Jaycox, Yile Dai, Anne E. Watkins, Suzanne Fischer, Nathan D. Grubaugh, Jon Klein, Eric Wang, Aaron M. Ring, Tianyang Mao, Patrick Wong, Akiko Iwasaki, Chaney C. Kalinich, Feimei Liu, Ting Zhou, Julio Silva, Benjamin Israelow, John Fournier, Andreas Coppi, Shuangge Ma, Albert I. Ko, Melissa Campbell, John D. Huck, Eric Song
Rok vydání: 2021
Předmět:
Zdroj: Nature. 595:283-288
ISSN: 1476-4687
0028-0836
Popis: COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, 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 profiling7 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.
Databáze: OpenAIRE
Externí odkaz: