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; Yehuda Shoenfeld

doi:10.1038/s41467-022-28905-5

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 SchumannAlexander 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, Yehuda Shoenfeld

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	1220
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-28905-5
State	Published - Dec 2022

ASJC Scopus subject areas

General
Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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Cabral-Marques, O., Halpert, G., Schimke, L. F., Ostrinski, Y., Vojdani, A., Baiocchi, G. C., Freire, P. P., Filgueiras, I. S., Zyskind, I., Lattin, M. T., Tran, F., Schreiber, S., Marques, A. H. C., Plaça, D. R., Fonseca, D. L. M., Humrich, J. Y., Müller, A., Giil, L. M., Graßhoff, H., ... Shoenfeld, Y. (2022). Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity. Nature communications, 13(1), [1220]. https://doi.org/10.1038/s41467-022-28905-5

Cabral-Marques, O, Halpert, G, Schimke, LF, Ostrinski, Y, Vojdani, A, Baiocchi, GC, Freire, PP, Filgueiras, IS, Zyskind, I, Lattin, MT, Tran, F, Schreiber, S, Marques, AHC, Plaça, DR, Fonseca, DLM, Humrich, JY, Müller, A, Giil, LM, Graßhoff, H, Schumann, A, Hackel, A, Junker, J, Meyer, C, Ochs, HD, Lavi, YB, Scheibenbogen, C, Dechend, R, Jurisica, I, Schulze-Forster, K, Silverberg, JI, Amital, H, Zimmerman, J, Heidecke, H, Rosenberg, AZ, Riemekasten, G & Shoenfeld, Y 2022, 'Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity', Nature communications, vol. 13, no. 1, 1220. https://doi.org/10.1038/s41467-022-28905-5

@article{3c1daf7ffcfc49ec95eb49c1f99155f3,

title = "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.",

author = "Otavio Cabral-Marques and Gilad Halpert and Schimke, {Lena F.} and Yuri Ostrinski and Aristo Vojdani and Baiocchi, {Gabriela Crispim} and Freire, {Paula Paccielli} and Filgueiras, {Igor Salerno} and Israel Zyskind and Lattin, {Miriam T.} and Florian Tran and Stefan Schreiber and Marques, {Alexandre H.C.} and Pla{\c c}a, {Desir{\'e}e Rodrigues} and Fonseca, {Dennyson Leandro M.} and Humrich, {Jens Y.} and Antje M{\"u}ller and Giil, {Lasse M.} and Hanna Gra{\ss}hoff and Anja Schumann and Alexander Hackel and Juliane Junker and Carlotta Meyer and Ochs, {Hans D.} and Lavi, {Yael Bublil} and Carmen Scheibenbogen and Ralf Dechend and Igor Jurisica and Kai Schulze-Forster and Silverberg, {Jonathan I.} and Howard Amital and Jason Zimmerman and Harry Heidecke and Rosenberg, {Avi Z.} and Gabriela Riemekasten and Yehuda Shoenfeld",

note = "Funding Information: We acknowledge the patients for participation in this study. We also thank the S{\~a}o Paulo Research Foundation (FAPESP grants: 2018/18886-9, 2020/01688-0, and 2020/07069-0 to O.C.M.; 2020/09146-1 to P.P.F.; 2020/16246-2 to D.L.M.F.; 2020/07972-1 to G.C.B., 2020/11710-2 to D.R.P.), and the Coordination for the Improvement of Higher Education Personnel (CAPES) Financial Code 001 (grant to ISF) for financial support. We acknowledge the Ontario Research Fund (grant #34876), Natural Sciences Research Council (NSERC #203475), Canada Foundation for Innovation (CFI #29272, #225404, #33536), and IBM. This work was also supported by the Deutsche Forschungsgemeinschaft (DFG) founding the Excellence Cluster Precision Medicine in Inflammation, project TI4 and CD1, by the COVID fund of Schleswig-Holstein as well as by DFG project RI 1056 11-1/2. This work was supported by the Bundesministerium f{\"u}r Bildung und Forschung [01EC1901D (MESINFLAME)]. We thank Prof. Dr. med. Tanja Lange from the Department of Rheumatology and Clinical Immunology at the University of L{\"u}beck, Germany for her advice to measure autoantibodies targeting the angiotensin-(1-7) receptor MAS1. We would like to acknowledge the contributions of Lev Rochel Bikur Cholim of Lakewood (led by Rabbi Yehuda Kasirer and Mrs. Leeba Prager) and their hundreds of volunteers who participated in collecting samples for this research. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-28905-5",

language = "English (US)",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity

AU - Cabral-Marques, Otavio

AU - Halpert, Gilad

AU - Schimke, Lena F.

AU - Ostrinski, Yuri

AU - Vojdani, Aristo

AU - Baiocchi, Gabriela Crispim

AU - Freire, Paula Paccielli

AU - Filgueiras, Igor Salerno

AU - Zyskind, Israel

AU - Lattin, Miriam T.

AU - Tran, Florian

AU - Schreiber, Stefan

AU - Marques, Alexandre H.C.

AU - Plaça, Desirée Rodrigues

AU - Fonseca, Dennyson Leandro M.

AU - Humrich, Jens Y.

AU - Müller, Antje

AU - Giil, Lasse M.

AU - Graßhoff, Hanna

AU - Schumann, Anja

AU - Hackel, Alexander

AU - Junker, Juliane

AU - Meyer, Carlotta

AU - Ochs, Hans D.

AU - Lavi, Yael Bublil

AU - Scheibenbogen, Carmen

AU - Dechend, Ralf

AU - Jurisica, Igor

AU - Schulze-Forster, Kai

AU - Silverberg, Jonathan I.

AU - Amital, Howard

AU - Zimmerman, Jason

AU - Heidecke, Harry

AU - Rosenberg, Avi Z.

AU - Riemekasten, Gabriela

AU - Shoenfeld, Yehuda

N1 - Funding Information: We acknowledge the patients for participation in this study. We also thank the São Paulo Research Foundation (FAPESP grants: 2018/18886-9, 2020/01688-0, and 2020/07069-0 to O.C.M.; 2020/09146-1 to P.P.F.; 2020/16246-2 to D.L.M.F.; 2020/07972-1 to G.C.B., 2020/11710-2 to D.R.P.), and the Coordination for the Improvement of Higher Education Personnel (CAPES) Financial Code 001 (grant to ISF) for financial support. We acknowledge the Ontario Research Fund (grant #34876), Natural Sciences Research Council (NSERC #203475), Canada Foundation for Innovation (CFI #29272, #225404, #33536), and IBM. This work was also supported by the Deutsche Forschungsgemeinschaft (DFG) founding the Excellence Cluster Precision Medicine in Inflammation, project TI4 and CD1, by the COVID fund of Schleswig-Holstein as well as by DFG project RI 1056 11-1/2. This work was supported by the Bundesministerium für Bildung und Forschung [01EC1901D (MESINFLAME)]. We thank Prof. Dr. med. Tanja Lange from the Department of Rheumatology and Clinical Immunology at the University of Lübeck, Germany for her advice to measure autoantibodies targeting the angiotensin-(1-7) receptor MAS1. We would like to acknowledge the contributions of Lev Rochel Bikur Cholim of Lakewood (led by Rabbi Yehuda Kasirer and Mrs. Leeba Prager) and their hundreds of volunteers who participated in collecting samples for this research. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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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JO - Nature Communications

JF - Nature Communications

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

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