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

ABSTRACT: 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.

SUBMITTER: Cabral-Marques O

PROVIDER: S-EPMC8907309 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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

Cabral-Marques Otavio O Halpert Gilad G Schimke Lena F LF Ostrinski Yuri Y Vojdani Aristo A Baiocchi Gabriela Crispim GC Freire Paula Paccielli PP Filgueiras Igor Salerno IS Zyskind Israel I Lattin Miriam T MT Tran Florian F Schreiber Stefan S Marques Alexandre H C AHC Plaça Desirée Rodrigues DR Fonseca Dennyson Leandro M DLM Humrich Jens Y JY Müller Antje A Giil Lasse M LM Graßhoff Hanna H Schumann Anja A Hackel Alexander A Junker Juliane J Meyer Carlotta C Ochs Hans D HD Lavi Yael Bublil YB Scheibenbogen Carmen C Dechend Ralf R Jurisica Igor I Schulze-Forster Kai K Silverberg Jonathan I JI Amital Howard H Zimmerman Jason J Heidecke Harry H Rosenberg Avi Z AZ Riemekasten Gabriela G Shoenfeld Yehuda Y

Nature communications 20220309 1

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 b ...[more]

PMID: 35264564

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Project description:IntroductionImpairment of the type I interferon (IFN-I) signaling pathway is associated with increased severity of COVID-19 disease. Here we have undertaken a systematic review and meta = analysis on the association between the severity of COVID-19 and IFN-1 autoantibodies (AAbs; aIFN-1, aIFN-α, aIFN-ω, and aIFN-β).MethodsFour databases, including Medline [PubMed], Embase, Web of Science, and Scopus, were systematically searched to find papers on the role of aIFN-1 and its subtype AAbs in the severity of COVID-19 infection. Data on the prevalence of aIFN-1, aIFN-α, aIFN-ω, and aIFN-β were pooled using random- or fixed-effects models. Subgroup analysis was performed based on disease severity. Odds ratios (OR) for COVID-19 disease outcome, including length of hospital stay, ICU admission and death, were calculated in relation to positive or negative plasma IFN-1 AAbs.ResultsA total of 33 studies with 13023 patients were included. The overall prevalence of circulating aIFN-1, aIFN-α, and aIFN-ω AAbs was 17.8 % [13.8, 22.8], 7.2 % [4.7, 10.9], and 4.4 % [2.1, 8.6], respectively, and the overall prevalence of neutralizing aIFN-1, aIFN-α, aIFN-ω, and aIFN-β AAbs was 7.1 % [4.9, 10.1], 7.5 % [5.9, 9.5], 8.0 % [5.7, 11.1] and 1.2 % [0.4, 3.5], respectively. Circulating aIFN-α (OR = 4.537 [2.247, 9.158]), neutralizing aIFN-α (O = 17.482 [8.899, 34.342]), and neutralizing aIFN-ω (OR = 12.529 [7.397, 21.222]) were significantly more frequent in critical/severe patients than in moderate/mild patients (p < 0.001 for all). Anti-IFN-1 was more common in male subjects (OR = 2.248 [1.366, 3.699], p = 0.001) and two COVID-19 outcomes including ICU admission (OR = 2.485 [1.409, 4.385], p = 0.002) and death (OR = 2.593 [1.199, 5.604], p = 0.015) occurred more frequently in patients with positive anti-IFN-1.Conclusion: aIFN-1 and its subtypes AAbs are associated with severe and critical COVID-19 disease and may be a predictive marker for a poor prognosis, particularly in men.

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

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

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