Diverse functional autoantibodies in patients with COVID-19

Eric Y. Wang, Tianyang Mao, Jon Klein, Yile Dai, John D. Huck, Jillian R. Jaycox, Feimei Liu, Ting Zhou, Benjamin Israelow, Patrick Wong, Andreas Coppi, Carolina Lucas, Julio Silva, Ji Eun Oh, Eric Song, Emily S. Perotti, Neil S. Zheng, Suzanne Fischer, Melissa Campbell, John B. Fournier, Anne L. Wyllie, Chantal B. F. Vogels, Isabel M. Ott, Chaney C. Kalinich, Mary E. Petrone, Anne E. Watkins, Charles Cruz, Shelli F. Farhadian, Wade L. Schulz, Shuangge Ma, Nathan D. Grubaugh, Albert I. Ko, Akiko Iwasaki () and Aaron M. Ring ()
Additional contact information
Eric Y. Wang: Yale School of Medicine
Tianyang Mao: Yale School of Medicine
Jon Klein: Yale School of Medicine
Yile Dai: Yale School of Medicine
John D. Huck: Yale School of Medicine
Jillian R. Jaycox: Yale School of Medicine
Feimei Liu: Yale School of Medicine
Ting Zhou: Yale School of Medicine
Benjamin Israelow: Yale School of Medicine
Patrick Wong: Yale School of Medicine
Andreas Coppi: Yale–New Haven Hospital
Carolina Lucas: Yale School of Medicine
Julio Silva: Yale School of Medicine
Ji Eun Oh: Yale School of Medicine
Eric Song: Yale School of Medicine
Emily S. Perotti: Yale School of Medicine
Neil S. Zheng: Yale School of Medicine
Suzanne Fischer: Yale School of Medicine
Melissa Campbell: Yale School of Medicine
John B. Fournier: Yale School of Medicine
Anne L. Wyllie: Yale School of Public Health
Chantal B. F. Vogels: Yale School of Public Health
Isabel M. Ott: Yale School of Public Health
Chaney C. Kalinich: Yale School of Public Health
Mary E. Petrone: Yale School of Public Health
Anne E. Watkins: Yale School of Public Health
Charles Cruz: Yale School of Medicine
Shelli F. Farhadian: Yale School of Medicine
Wade L. Schulz: Yale–New Haven Hospital
Shuangge Ma: Yale School of Public Health
Nathan D. Grubaugh: Yale School of Public Health
Albert I. Ko: Yale School of Medicine
Akiko Iwasaki: Yale School of Medicine
Aaron M. Ring: Yale School of Medicine

Nature, 2021, vol. 595, issue 7866, 283-288

Abstract: Abstract 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (10)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03631-y Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:595:y:2021:i:7866:d:10.1038_s41586-021-03631-y

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03631-y

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().