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

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. Lattin, Florian Tran, Stefan Schreiber, Alexandre H. C. Marques, Desirée Rodrigues Plaça, Dennyson Leandro M. Fonseca, Jens Y. Humrich, Antje Müller, Lasse M. Giil, Hanna Graßhoff, Anja Schumann, Alexander Hackel, Juliane Junker, Carlotta Meyer, Hans D. Ochs, Yael Bublil Lavi, Carmen Scheibenbogen, Ralf Dechend, Igor Jurisica, Kai Schulze-Forster, Jonathan I. Silverberg, Howard Amital, Jason Zimmerman, Harry Heidecke, Avi Z. Rosenberg, Gabriela Riemekasten () and Yehuda Shoenfeld ()
Additional contact information
Otavio Cabral-Marques: University of São Paulo
Gilad Halpert: Sheba Medical Center
Lena F. Schimke: University of São Paulo
Yuri Ostrinski: Sheba Medical Center
Aristo Vojdani: Immunosciences Laboratory, Inc.
Gabriela Crispim Baiocchi: University of São Paulo
Paula Paccielli Freire: University of São Paulo
Igor Salerno Filgueiras: University of São Paulo
Israel Zyskind: NYU Langone Medical Center
Miriam T. Lattin: Yeshiva University
Florian Tran: University Medical Center Schleswig-Holstein Campus Kiel
Stefan Schreiber: University Medical Center Schleswig-Holstein Campus Kiel
Alexandre H. C. Marques: University of São Paulo
Desirée Rodrigues Plaça: University of São Paulo
Dennyson Leandro M. Fonseca: University of São Paulo
Jens Y. Humrich: University Medical Center Schleswig-Holstein Campus Lübeck
Antje Müller: University Medical Center Schleswig-Holstein Campus Lübeck
Lasse M. Giil: Haraldsplass Deaconess Hospital
Hanna Graßhoff: University Medical Center Schleswig-Holstein Campus Lübeck
Anja Schumann: University Medical Center Schleswig-Holstein Campus Lübeck
Alexander Hackel: University Medical Center Schleswig-Holstein Campus Lübeck
Juliane Junker: CellTrend Gesellschaft mit beschränkter Haftung (GmbH)
Carlotta Meyer: CellTrend Gesellschaft mit beschränkter Haftung (GmbH)
Hans D. Ochs: University of Washington School of Medicine, and Seattle Children’s Research Institute
Yael Bublil Lavi: Tel-Aviv University
Carmen Scheibenbogen: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Ralf Dechend: Department of Cardiology and Nephrology
Igor Jurisica: University of Toronto
Kai Schulze-Forster: CellTrend Gesellschaft mit beschränkter Haftung (GmbH)
Jonathan I. Silverberg: George Washington University
Howard Amital: Sheba Medical Center
Jason Zimmerman: Maimonides Medical Center
Harry Heidecke: CellTrend Gesellschaft mit beschränkter Haftung (GmbH)
Avi Z. Rosenberg: Johns Hopkins University
Gabriela Riemekasten: University Medical Center Schleswig-Holstein Campus Lübeck
Yehuda Shoenfeld: Sheba Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28905-5

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