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^*

^*Corresponding author for this work

Clinic of Rheumatology

31 Citations (Scopus)

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
Article number	1220
Journal	Nature Communications
Volume	13
Issue number	1
ISSN	1751-8628
DOIs	https://doi.org/10.1038/s41467-022-28905-5
Publication status	Published - 12.2022

Funding

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.

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

2.22-18 Rheumatology
2.21-05 Immunology

Coronavirus related work

Research on SARS-CoV-2 / COVID-19

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-022-28905-5

Cite this

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), Article 1220. https://doi.org/10.1038/s41467-022-28905-5

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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 = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

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

language = "English",

volume = "13",

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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

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

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.

UR - https://www.scopus.com/pages/publications/85126081158

U2 - 10.1038/s41467-022-28905-5

DO - 10.1038/s41467-022-28905-5

M3 - Journal articles

C2 - 35264564

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SN - 1751-8628

VL - 13

JO - Nature Communications

JF - Nature Communications

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M1 - 1220

ER -

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

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

Coronavirus related work

UN SDGs

Access to Document

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