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Diverse functional autoantibodies in patients with COVID-19

Author

Listed:
  • 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
    Yale School of Medicine)

  • Shuangge Ma

    (Yale School of Public Health)

  • Nathan D. Grubaugh

    (Yale School of Public Health)

  • Albert I. Ko

    (Yale School of Medicine
    Yale School of Public Health)

  • Akiko Iwasaki

    (Yale School of Medicine
    Yale School of Public Health
    Howard Hughes Medical Institute)

  • Aaron M. Ring

    (Yale School of Medicine
    Department of Pharmacology, Yale School of Medicine)

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.

Suggested Citation

  • 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 Eu, 2021. "Diverse functional autoantibodies in patients with COVID-19," Nature, Nature, vol. 595(7866), pages 283-288, July.
  • Handle: RePEc:nat:nature:v:595:y:2021:i:7866:d:10.1038_s41586-021-03631-y
    DOI: 10.1038/s41586-021-03631-y
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    Citations

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    Cited by:

    1. Juliana Lapa & Davi Rosa & João Pedro Lima Mendes & Rodolfo Deusdará & Gustavo Adolfo Sierra Romero, 2023. "Prevalence and Associated Factors of Post-COVID-19 Syndrome in a Brazilian Cohort after 3 and 6 Months of Hospital Discharge," IJERPH, MDPI, vol. 20(1), pages 1-12, January.
    2. Rúbens Prince dos Santos Alves & Julia Timis & Robyn Miller & Kristen Valentine & Paolla Beatriz Almeida Pinto & Andrew Gonzalez & Jose Angel Regla-Nava & Erin Maule & Michael N. Nguyen & Norazizah Sh, 2024. "Human coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Otavio Cabral-Marques & Gilad Halpert & Lena F. Schimke & Yuri Ostrinski & Aristo Vojdani & Gabriela Crispim Baiocchi & Paula Paccielli Freire & Igor Salerno Filgueiras & Israel Zyskind & Miriam T. La, 2022. "Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. August F. Jernbom & Lovisa Skoglund & Elisa Pin & Ronald Sjöberg & Hanna Tegel & Sophia Hober & Elham Rostami & Annica Rasmusson & Janet L. Cunningham & Sebastian Havervall & Charlotte Thålin & Anna M, 2024. "Prevalent and persistent new-onset autoantibodies in mild to severe COVID-19," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Jillian R. Jaycox & Carolina Lucas & Inci Yildirim & Yile Dai & Eric Y. Wang & Valter Monteiro & Sandra Lord & Jeffrey Carlin & Mariko Kita & Jane H. Buckner & Shuangge Ma & Melissa Campbell & Albert , 2023. "SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    6. Brent Appelman & Braeden T. Charlton & Richie P. Goulding & Tom J. Kerkhoff & Ellen A. Breedveld & Wendy Noort & Carla Offringa & Frank W. Bloemers & Michel Weeghel & Bauke V. Schomakers & Pedro Coelh, 2024. "Muscle abnormalities worsen after post-exertional malaise in long COVID," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    7. Hideki Ogura & Jin Gohda & Xiuyuan Lu & Mizuki Yamamoto & Yoshio Takesue & Aoi Son & Sadayuki Doi & Kazuyuki Matsushita & Fumitaka Isobe & Yoshihiro Fukuda & Tai-Ping Huang & Takamasa Ueno & Naomi Mam, 2022. "Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Jakob Ankerhold & Sebastian Giese & Philipp Kolb & Andrea Maul-Pavicic & Reinhard E. Voll & Nathalie Göppert & Kevin Ciminski & Clemens Kreutz & Achim Lother & Ulrich Salzer & Wolfgang Bildl & Tim Wel, 2022. "Circulating multimeric immune complexes contribute to immunopathology in COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. André Santa Cruz & Ana Mendes-Frias & Marne Azarias-da-Silva & Sónia André & Ana Isabel Oliveira & Olga Pires & Marta Mendes & Bárbara Oliveira & Marta Braga & Joana Rita Lopes & Rui Domingues & Ricar, 2023. "Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+β7 integrin+ T cells and anti-SARS-CoV-2 IgA response," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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