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

Otavio Cabral-Marques, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. otavio.cmarques@usp.br.
Gilad Halpert, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
Lena F. Schimke, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Yuri Ostrinski, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
Aristo Vojdani, Department of Immunology, Immunosciences Laboratory, Inc., Los Angeles, CA, United States.
Gabriela Crispim Baiocchi, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Paula Paccielli Freire, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Igor Salerno Filgueiras, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Israel Zyskind, Department of Pediatrics, NYU Langone Medical Center, New York, NY, USA.
Miriam T. Lattin, Department of Biology, Yeshiva University, Manhatten, NY, USA.
Florian Tran, Department of Internal Medicine I, University Medical Center Schleswig-Holstein Campus Kiel, Kiel, Germany.
Stefan Schreiber, Department of Internal Medicine I, University Medical Center Schleswig-Holstein Campus Kiel, Kiel, Germany.
Alexandre H. Marques, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Desirée Rodrigues Plaça, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Dennyson Leandro Fonseca, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Jens Y. Humrich, Department of Rheumatology, University Medical Center Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
Antje Müller, Department of Rheumatology, University Medical Center Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
Lasse M. Giil, Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
Hanna Graßhoff, Department of Rheumatology, University Medical Center Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
Anja Schumann, Department of Rheumatology, University Medical Center Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
Alexander Hackel, Department of Rheumatology, University Medical Center Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
Juliane Junker, CellTrend Gesellschaft mit beschränkter Haftung (GmbH), Luckenwalde, Germany.
Carlotta Meyer, CellTrend Gesellschaft mit beschränkter Haftung (GmbH), Luckenwalde, Germany.
Hans D. Ochs, Department of Pediatrics, University of Washington School of Medicine, and Seattle Children's Research Institute, Seattle, WA, USA.
Yael Bublil Lavi, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Carmen Scheibenbogen, Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Ralf Dechend, Experimental and Clinical Research Center, a collaboration of Max Delbruck Center for Molecular Medicine and Charité Universitätsmedizin, and HELIOS Clinic, Department of Cardiology and Nephrology, Berlin, 13125, Germany.
Igor Jurisica, Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, UHN; Data Science Discovery Centre, Krembil Research Institute, UHN, Departments of Medical Biophysics and Computer Science, University of Toronto, Toronto, Canada.
Kai Schulze-Forster, CellTrend Gesellschaft mit beschränkter Haftung (GmbH), Luckenwalde, Germany.
Jonathan I. Silverberg, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Howard Amital, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
Jason Zimmerman, Maimonides Medical Center, Brooklyn, NY, USA.

Document Type

Journal Article

Publication Date

3-9-2022

Journal

Nature communications

Volume

13

Issue

1

DOI

10.1038/s41467-022-28905-5

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.

Department

Dermatology

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