High-throughput identification of autoantibodies that target the human exoproteome

Wang, Eric Y.; Dai, Yile; Schmitt, Monica M.; Dong, Mei X.; Ferré, Elise M. N.; Liu, Feimei; Yang, Yi; González-Hernández, Jaime A.; Meffre, Eric; Hinchcliff, Monique; Koumpouras, Fotios; Lionakis, Michail S; Ring, Aaron M.

doi:10.1016/j.crmeth.2022.100172

Cited by 31 publications

(51 citation statements)

References 75 publications

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“…Thus, these autoantibodies possibly potentialize the signaling triggered by their natural ligand, promoting the migration of immune cells, such as CD4+ and CD8+ T cells that are critical for both the killing of SARS-CoV-2 in the lung and deleterious hyperinflammation 56 , 57 . Regardless that we did not investigate the activity of autoantibodies on their targets, the results of our work underscore those of recent studies 3 , 6 , 10 – 12 that have reported the generation of autoantibodies following SARS-CoV-2 infection. Importantly, our data indicate that an additional immunopathological layer is present in which autoantibodies targeting GPCRs and RAS-related molecules are associated with COVID-19 burden.…”

Section: Discussionsupporting

confidence: 78%

“…Most recently, a wide range of autoantibodies in patients with COVID-19 have been characterized using rapid extracellular antigen profiling (REAP) 11 . This is a technology that allows the comprehensive and high-throughput identification of autoantibodies by recognizing 2770 extracellular and secreted protein components of the exoproteome (extracellular protein epitopes) 12 . Wang et al 11 showed that COVID-19 patients have multiple autoantibodies against the exoproteome.…”

Section: Introductionmentioning

confidence: 99%

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Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity

et al. 2022

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COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand the role of these immune globulins in the pathogenesis of the disease, it is important to explore the autoantibody spectra. Here we show, by a cross-sectional study of 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate with the clinical severity of COVID-19. Patients with moderate and severe disease are characterized by higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Among the anti-GPCR autoantibodies, machine learning classification identifies the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as targets for antibodies with the strongest association to disease severity. Besides antibody levels, autoantibody network signatures are also changing in patients with intermediate or high disease severity. Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity

et al. 2022

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“…Participant IgG isolation and REAP selections were performed as previously described 21, 49 . Briefly, IgG was purified from participant plasma using protein G magnetic beads followed by adsorption to yeast transformed with the pDD003 empty vector to remove yeast-reactive IgG.…”

Section: Methodsmentioning

confidence: 99%

“…REAP Library Expansion. The initial yeast library (Exo201) was generated as previously described 21,49 . In Exo201, only extracellular domains >49 amino acids in length were included in the library.…”

Section: Rapid Extracellular Antigen Profiling (Reap)mentioning

confidence: 99%

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Distinguishing features of Long COVID identified through immune profiling

Klein

Wood

Jaycox

et al. 2022

Preprint

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209

220

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SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.

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Autoantibodies in COVID‐19 and Other Viral Diseases: Molecular, Cellular, and Clinical Perspectives

Chatterjee,

Bhattacharya,

Saxena

et al. 2024

Reviews in Medical Virology

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Autoantibodies are immune system‐produced antibodies that wrongly target the body's cells and tissues for attack. The COVID‐19 pandemic has made it possible to link autoantibodies to both the severity of pathogenic infection and the emergence of several autoimmune diseases after recovery from the infection. An overview of autoimmune disorders and the function of autoantibodies in COVID‐19 and other infectious diseases are discussed in this review article. We also investigated the different categories of autoantibodies found in COVID‐19 and other infectious diseases including the potential pathways by which they contribute to the severity of the illness. Additionally, it also highlights the probable connection between vaccine‐induced autoantibodies and their adverse outcomes. The review also discusses the therapeutic perspectives of autoantibodies. This paper advances our knowledge about the intricate interaction between autoantibodies and COVID‐19 by thoroughly assessing the most recent findings.

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High-throughput identification of autoantibodies that target the human exoproteome

Cited by 31 publications

References 75 publications

Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity

Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity

Distinguishing features of Long COVID identified through immune profiling

Autoantibodies in COVID‐19 and Other Viral Diseases: Molecular, Cellular, and Clinical Perspectives

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