Diverse functional autoantibodies in patients with COVID-19

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Wang, Eric Y. / Mao, Tianyang / Klein, Jon / Dai, Yile / Huck, John D. / Jaycox, Jillian R. / Liu, Feimei / Zhou, Ting / Israelow, Benjamin / Wong, Patrick / Coppi, Andreas / Lucas, Carolina / Silva, Julio / Oh, Ji Eunresearcher / Song, Eric / Perotti, Emily S. / Zheng, Neil S. / Fischer, Suzanne / Campbell, Melissa / Fournier, John B. / Wyllie, Anne L. / Vogels, Chantal B. F. / Ott, Isabel M. / Kalinich, Chaney C. / Petrone, Mary E. / Watkins, Anne E. / Obaid, Abeer / Moore, Adam J. / Casanovas-Massana, Arnau / Lu-Culligan, Alice / Nelson, Allison / Nunez, Angela / Martin, Anjelica / Geng, Bertie / Odio, Camila D. / Harden, Christina A. / Todeasa, Codruta / Jensen, Cole / Kim, Daniel / McDonald, David / Shepard, Denise / Courchaine, Edward / White, Elizabeth B. / Silva, Erin / Kudo, Eriko / DeIuliis, Giuseppe / Rahming, Harold / Park, Hong-Jai / Matos, Irene / Nouws, Jessica / Valdez, Jordan / Lim, Joseph / Rose, Kadi-Ann / Anastasio, Kelly / Brower, Kristina / Glick, Laura / Sharma, Lokesh / Sewanan, Lorenzo / Knaggs, Lynda / Minasyan, Maksym / Batsu, Maria / Kuang, Maxine / Nakahata, Maura / Linehan, Melissa / Askenase, Michael H. / Simonov, Michael / Smolgovsky, Mikhail / Sonnert, Nicole / Naushad, Nida / Vijayakumar, Pavithra / Martinello, Rick / Datta, Rupak / Handoko, Ryan / Bermejo, Santos / Prophet, Sarah / Bickerton, Sean / Velazquez, Sofia / Rice, Tyler / Khoury-Hanold, William / Peng, Xiaohua / Yang, Yexin / Cao, Yiyun / Strong, Yvette / Dela Cruz, Charles / Farhadian, Shelli F. / Schulz, Wade L. / Ma, Shuangge / Grubaugh, Nathan D. / Ko, Albert I. / Iwasaki, Akiko / Ring, Aaron M.
COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses 1-8 . While pathological innate immune activation is well documented in severe disease 1 , the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the "exoproteome"). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with 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 signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.
Publisher
NATURE RESEARCH
Issue Date
2021-05
Language
English
Citation

NATURE, v.595, pp.283 - 288

ISSN
0028-0836
DOI
10.1038/s41586-021-03631-y
URI
http://hdl.handle.net/10203/287108
Appears in Collection
MSE-Journal Papers(저널논문)
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