Advancing research on regulatory autoantibodies targeting GPCRs: Insights from the 5th international symposium

Otavio Cabral-Marques¹, Lena F Schimke², Guido Moll³, Igor Salerno Filgueiras⁴, Adriel Leal Nóbile⁵, Anny Silva Adri⁵, Fernando Yuri Nery do Vale⁵, Júlia Nakanishi Usuda⁵, Yohan Lucas Gonçalves Corrêa⁵, Débora Albuquerque⁶, Roseane Galdioli Nava⁶, Ronaldy Santana Santos⁵, Haroldo Dutra Dias², Hélio Fernandes Silva⁷, Pedro Batista Marconi⁸, Rusan Catar⁹, Michael Adu-Gyamfi⁹, Pinchao Wang⁹, Taj Ali Khan¹⁰, Alexander M Hackel¹¹, Anja Leheis¹¹, Anja Stähle¹¹, Antje Müller¹¹, Carolin Schmidt¹¹, Chiara Radunovic¹¹, El-Baraa Adjailia¹¹, Hanna Grasshoff¹¹, Jens Y Humrich¹¹, Jonas Menz¹¹, Konstantinos Fourlakis¹¹, Maike Winziers¹¹, Maj Jäpel¹¹, Manuel Vincent Wegner¹¹, Peter Lamprecht¹¹, Relana Nieberding¹¹, Reza Akbarzadeh¹¹, Sabrina Arnold¹¹, Sebastian Jendrek¹¹, Sebastian Klapa¹¹, Solveig Augustin¹¹, Sophie Biedermann¹¹, Susanne Schinke¹¹, Patrick Scheerer¹², Matthias Endres¹³, Kai Schulze-Forster¹⁴, Friedemann Paul¹⁵, Xinhua Yu¹⁶, Franziska Sotzny¹⁷, Thomas P Sakmar¹⁸, Miroslaw Banasik¹⁹, Aiden Haghikia²⁰, Markus H Hoffmann²¹, Dmitry Veprintsev²², Torsten Witte²³, Rodrigo J S Dalmolin²⁴, Hans D Ochs²⁵, Harald Heidecke¹⁴, Carmen Scheibenbogen¹⁷, Yehuda Shoenfeld²⁶, Gabriela Riemekasten²⁷

Affiliations

¹ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo School of Medicine, São Paulo, Brazil; Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sao Paulo, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics, University of Sao Paulo, Sao Paulo, Brazil; D'Or Institute for Research and Education, Rio de Janeiro, Brazil. Electronic address: otavio.cmarques@gmail.com.
² Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo School of Medicine, São Paulo, Brazil.
³ BIH Center for Regenerative Therapies (BCRT) and Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany; Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁴ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
⁵ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
⁶ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics, University of Sao Paulo, Sao Paulo, Brazil.
⁷ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Bauru Medical School, University of São Paulo, Bauru, Brazil.
⁸ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; D'Or Institute for Research and Education, Rio de Janeiro, Brazil.
⁹ Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹⁰ Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar, Pakistan.
¹¹ Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
¹² Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics, Group Structural Biology of Cellular Signaling, Berlin, Germany.
¹³ Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Berlin, Germany; Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), Partner Site Berlin, Berlin, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany; German Center for Mental Health (DZPG), Partner Site Berlin, Berlin, Germany.
¹⁴ CellTrend GmbH, Luckenwalde, Germany.
¹⁵ Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Berlin, Germany; Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin, Germany; Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
¹⁶ Priority Area Chronic Lung Diseases, Research Center Borstel (RCB), Member of the German Center for Lung Research (DZL), Borstel, Germany.
¹⁷ Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu Berlin, Berlin, Germany.
¹⁸ Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, New York, NY, USA.
¹⁹ Department of Nephrology, Transplantation Medicine and Internal Diseases, Wroclaw Medical University, Wroclaw, Poland.
²⁰ Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany.
²¹ Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
²² Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom; Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham and University of Nottingham, Nottingham, United Kingdom; Z7 Biotech Ltd., Nottingham, United Kingdom.
²³ Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
²⁴ Bioinformatics Multidisciplinary Environment, Federal University of Rio Grande do Norte, Brazil.
²⁵ Department of Pediatrics, University of Washington School of Medicine, and Seattle Children's Research Institute, Seattle, WA, USA.
²⁶ Reichman University, Herzelia, Israel; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5265601, Israel.
²⁷ Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany. Electronic address: gabriela.riemekasten@uksh.de.

PMID: 40543860
DOI: 10.1016/j.autrev.2025.103855

Free article

Review

Advancing research on regulatory autoantibodies targeting GPCRs: Insights from the 5th international symposium

Otavio Cabral-Marques et al. Autoimmun Rev. 2025.

Free article

. 2025 Aug 29;24(9):103855.

doi: 10.1016/j.autrev.2025.103855. Epub 2025 Jun 19.

Authors

Affiliations

¹ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo School of Medicine, São Paulo, Brazil; Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sao Paulo, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics, University of Sao Paulo, Sao Paulo, Brazil; D'Or Institute for Research and Education, Rio de Janeiro, Brazil. Electronic address: otavio.cmarques@gmail.com.
² Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo School of Medicine, São Paulo, Brazil.
³ BIH Center for Regenerative Therapies (BCRT) and Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany; Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁴ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
⁵ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
⁶ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics, University of Sao Paulo, Sao Paulo, Brazil.
⁷ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; Bauru Medical School, University of São Paulo, Bauru, Brazil.
⁸ Laboratory of Psychoneuroimmunology, Selye Lab, University of São Paulo School of Medicine, São Paulo, Brazil; D'Or Institute for Research and Education, Rio de Janeiro, Brazil.
⁹ Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹⁰ Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar, Pakistan.
¹¹ Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
¹² Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics, Group Structural Biology of Cellular Signaling, Berlin, Germany.
¹³ Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Berlin, Germany; Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), Partner Site Berlin, Berlin, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany; German Center for Mental Health (DZPG), Partner Site Berlin, Berlin, Germany.
¹⁴ CellTrend GmbH, Luckenwalde, Germany.
¹⁵ Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Berlin, Germany; Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin, Germany; Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
¹⁶ Priority Area Chronic Lung Diseases, Research Center Borstel (RCB), Member of the German Center for Lung Research (DZL), Borstel, Germany.
¹⁷ Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu Berlin, Berlin, Germany.
¹⁸ Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, New York, NY, USA.
¹⁹ Department of Nephrology, Transplantation Medicine and Internal Diseases, Wroclaw Medical University, Wroclaw, Poland.
²⁰ Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany.
²¹ Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
²² Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom; Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham and University of Nottingham, Nottingham, United Kingdom; Z7 Biotech Ltd., Nottingham, United Kingdom.
²³ Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
²⁴ Bioinformatics Multidisciplinary Environment, Federal University of Rio Grande do Norte, Brazil.
²⁵ Department of Pediatrics, University of Washington School of Medicine, and Seattle Children's Research Institute, Seattle, WA, USA.
²⁶ Reichman University, Herzelia, Israel; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5265601, Israel.
²⁷ Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany. Electronic address: gabriela.riemekasten@uksh.de.

PMID: 40543860
DOI: 10.1016/j.autrev.2025.103855

Abstract

The 5th International Symposium on Regulatory Autoantibodies Targeting GPCR (RAB-GPCRs) advanced the understanding of the significant role played by autoantibodies targeting G-protein-coupled receptors (GPCRs) in various human diseases. Once considered passive markers, RAB-GPCRs are now recognized as active modulators of cellular signaling, immune regulation, and inflammation. The symposium highlighted their involvement in multiple prominent pathologies, including autoimmune diseases, cardio- and cerebrovascular diseases, and neuroimmunologic disorders such as myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 syndrome (ME/CFS/PCS), as well as solid organ and hematopoietic stem cell transplantation (SOT/HSCT). Experts from rheumatology, immunology, and neurology presented interdisciplinary discussions on the potential of RAB-GPCRs as biomarkers and therapeutic targets. Advances in screening methods, biomarker identification, and therapeutic strategies were shared, emphasizing their diagnostic potential and application in novel therapeutic interventions. This report summarizes key insights from the symposium, particularly focusing on the modulatory properties of RAB-GPCRs and their relevance in both immune-mediated diseases and other pathologies (e.g., vascular, degenerative) that are traditionally not considered primarily immune-mediated. Ongoing research is expected to further establish these autoantibodies as crucial components in disease modulation and systems biology contexts, offering new opportunities for precision medicine and improved clinical outcomes in immune-related disorders.

Keywords: Biomarkers; G-protein coupled receptors (GPCRs); Immune regulation; Regulatory autoantibodies (RABs); Therapeutic targets.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Otavio Cabral Marques reports financial support was provided by State of Sao Paulo Research Foundation. Otavio Cabral Marques reports a relationship with State of Sao Paulo Research Foundation that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Advancing research on regulatory autoantibodies targeting GPCRs: Insights from the 5th international symposium

Affiliations

Advancing research on regulatory autoantibodies targeting GPCRs: Insights from the 5th international symposium

Authors

Affiliations

Abstract

Conflict of interest statement

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