Diverse Functional Autoantibodies in Patients with COVID-19
By Eric Y. Wang, Tianyang Mao, J. Klein, Yile Dai, J. Huck, Jillian R. Jaycox, Feimei Liu, Ting Zhou, Benjamin Israelow, P. Wong and 81 more. Nature, 2020
886 citations recorded by the source corpus.
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. Rapid extracellular antigen profiling of a cohort of 194 individuals infected with SARS-CoV-2 uncovers diverse autoantibody responses that affect COVID-19 disease severity, progression and clinical and immunological characteristics.
Subfields: Infectious Diseases, Neurology
View Paper: https://www.semanticscholar.org/paper/d6510182993933494d8a76254bd2373b1809edde
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Citations in the corpus
- Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms (2021, methodology): “Wang et al. (2020) used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARSCoV-2 infected COVID-19 patients for autoantibodies against 2,770 extracellular and secreted proteins (the exoproteome).”
- Multiple early factors anticipate post-acute COVID-19 sequelae (2022, positive): “Auto-antibodies anticorrelate with anti-SARS-CoV-2 antibodies and are associated with distinct patterns of PASC AutoAbs, especially those that neutralize type I interferons (IFNs), have been reported to be associated with immune dysfunction and COVID-19 mortality (Bastard et al., 2021; Wang et al., ”
- Distinguishing features of long COVID identified through immune profiling (2022, methodology): “REAP scores were calculated as previously described 16,69 .”