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Diverse Functional Autoantibodies in Patients with COVID-19

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. H...

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Autores principales: Wang, Eric Y., Mao, Tianyang, Klein, Jon, Dai, Yile, Huck, John D., Liu, Feimei, Zheng, Neil S., Zhou, Ting, Israelow, Benjamin, Wong, Patrick, Lucas, Carolina, Silva, Julio, Oh, Ji Eun, Song, Eric, Perotti, Emily 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., Cruz, Charles Dela, Farhadian, Shelli F., Schulz, Wade L., Grubaugh, Nathan D., Ko, Albert I., Iwasaki, Akiko, Ring, Aaron M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7743105/
https://www.ncbi.nlm.nih.gov/pubmed/33330894
http://dx.doi.org/10.1101/2020.12.10.20247205
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author Wang, Eric Y.
Mao, Tianyang
Klein, Jon
Dai, Yile
Huck, John D.
Liu, Feimei
Zheng, Neil S.
Zhou, Ting
Israelow, Benjamin
Wong, Patrick
Lucas, Carolina
Silva, Julio
Oh, Ji Eun
Song, Eric
Perotti, Emily 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.
Cruz, Charles Dela
Farhadian, Shelli F.
Schulz, Wade L.
Grubaugh, Nathan D.
Ko, Albert I.
Iwasaki, Akiko
Ring, Aaron M.
author_facet Wang, Eric Y.
Mao, Tianyang
Klein, Jon
Dai, Yile
Huck, John D.
Liu, Feimei
Zheng, Neil S.
Zhou, Ting
Israelow, Benjamin
Wong, Patrick
Lucas, Carolina
Silva, Julio
Oh, Ji Eun
Song, Eric
Perotti, Emily 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.
Cruz, Charles Dela
Farhadian, Shelli F.
Schulz, Wade L.
Grubaugh, Nathan D.
Ko, Albert I.
Iwasaki, Akiko
Ring, Aaron M.
author_sort Wang, Eric Y.
collection PubMed
description 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.
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spelling pubmed-77431052020-12-17 Diverse Functional Autoantibodies in Patients with COVID-19 Wang, Eric Y. Mao, Tianyang Klein, Jon Dai, Yile Huck, John D. Liu, Feimei Zheng, Neil S. Zhou, Ting Israelow, Benjamin Wong, Patrick Lucas, Carolina Silva, Julio Oh, Ji Eun Song, Eric Perotti, Emily 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. Cruz, Charles Dela Farhadian, Shelli F. Schulz, Wade L. Grubaugh, Nathan D. Ko, Albert I. Iwasaki, Akiko Ring, Aaron M. medRxiv Article 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. Cold Spring Harbor Laboratory 2021-02-01 /pmc/articles/PMC7743105/ /pubmed/33330894 http://dx.doi.org/10.1101/2020.12.10.20247205 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Wang, Eric Y.
Mao, Tianyang
Klein, Jon
Dai, Yile
Huck, John D.
Liu, Feimei
Zheng, Neil S.
Zhou, Ting
Israelow, Benjamin
Wong, Patrick
Lucas, Carolina
Silva, Julio
Oh, Ji Eun
Song, Eric
Perotti, Emily 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.
Cruz, Charles Dela
Farhadian, Shelli F.
Schulz, Wade L.
Grubaugh, Nathan D.
Ko, Albert I.
Iwasaki, Akiko
Ring, Aaron M.
Diverse Functional Autoantibodies in Patients with COVID-19
title Diverse Functional Autoantibodies in Patients with COVID-19
title_full Diverse Functional Autoantibodies in Patients with COVID-19
title_fullStr Diverse Functional Autoantibodies in Patients with COVID-19
title_full_unstemmed Diverse Functional Autoantibodies in Patients with COVID-19
title_short Diverse Functional Autoantibodies in Patients with COVID-19
title_sort diverse functional autoantibodies in patients with covid-19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7743105/
https://www.ncbi.nlm.nih.gov/pubmed/33330894
http://dx.doi.org/10.1101/2020.12.10.20247205
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