Journal article

GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis.

  • Cabral-Marques O Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany. otavio.cmarques@gmail.com.
  • Marques A Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany.
  • Giil LM Deaconess Hospital, University of Bergen, 5006, Bergen, Norway.
  • De Vito R Department of Computer Science, Princeton University, Princeton, NJ, 08540, USA.
  • Rademacher J Department of Gastroenterology, Infectiology and Rheumatology, Charité University Hospital, Berlin, 12203, Germany.
  • Günther J Dept. of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, 10117, Germany.
  • Lange T Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany.
  • Humrich JY Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany.
  • Klapa S Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany.
  • Schinke S Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany.
  • Schimke LF Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany.
  • Marschner G Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany.
  • Pitann S Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany.
  • Adler S University Hospital and University of Bern, Bern, 3012, Switzerland.
  • Dechend R Experimental and Clinical Research Center, a collaboration of Max Delbruck Center for Molecular Medicine and Charité Universitätsmedizin, Berlin, 13125, Germany.
  • Müller DN Experimental and Clinical Research Center, a collaboration of Max Delbruck Center for Molecular Medicine and Charité Universitätsmedizin, Berlin, 13125, Germany.
  • Braicu I Department of Nephrology and Cardiovascular Research, Campus Virchow, Charité University Hospital, Berlin, 13353, Germany.
  • Sehouli J Department of Gynecology, Charité University Hospital, Berlin and Tumor Bank Ovarian Cancer Network (TOC), Berlin, 13353, Germany.
  • Schulze-Forster K Department of Urology, Charité University Hospital, Berlin, 10117, Germany.
  • Trippel T Dept. of Internal Medicine & Cardiology, Charité University Hospital, Berlin, 13353, Germany.
  • Scheibenbogen C Institute for Medical Immunology, Charité University Hospital Berlin, Campus Virchow, Berlin, 10117, Germany.
  • Staff A University of Oslo and Oslo University Hospital, 0372, Oslo, Norway.
  • Mertens PR University Clinic for Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, Magdeburg, 39106, Germany.
  • Löbel M Institute for Medical Immunology, Charité University Hospital Berlin, Campus Virchow, Berlin, 10117, Germany.
  • Mastroianni J Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Albert Ludwigs University (ALU) of Freiburg, Freiburg, 79106, Germany.
  • Plattfaut C Section Experimental Oncology, University Hospital and Medical School (UKSH), University of Lübeck, Lübeck, 23538, Germany.
  • Gieseler F Section Experimental Oncology, University Hospital and Medical School (UKSH), University of Lübeck, Lübeck, 23538, Germany.
  • Dragun D Department of Nephrology and Cardiovascular Research, Campus Virchow, Charité University Hospital, Berlin, 13353, Germany.
  • Engelhardt BE Department of Computer Science, Princeton University, Princeton, NJ, 08540, USA.
  • Fernandez-Cabezudo MJ Department of Biochemistry College of Medicine and Health Sciences, UAE University, Al Ain, 17666, United Arab Emirates.
  • Ochs HD Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Research Institute, Seattle, WA, 98191, USA.
  • Al-Ramadi BK Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, 17666, United Arab Emirates.
  • Lamprecht P Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany.
  • Mueller A Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany.
  • Heidecke H Department of Urology, Charité University Hospital, Berlin, 10117, Germany.
  • Riemekasten G Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, 23538, Germany. gabriela.riemekasten@uksh.de.
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  • 2018-12-08
Published in:
  • Nature communications. - 2018
English Autoantibodies have been associated with autoimmune diseases. However, studies have identified autoantibodies in healthy donors (HD) who do not develop autoimmune disorders. Here we provide evidence of a network of immunoglobulin G (IgG) autoantibodies targeting G protein-coupled receptors (GPCR) in HD compared to patients with systemic sclerosis, Alzheimer's disease, and ovarian cancer. Sex, age and pathological conditions affect autoantibody correlation and hierarchical clustering signatures, yet many of the correlations are shared across all groups, indicating alterations to homeostasis. Furthermore, we identify relationships between autoantibodies targeting structurally and functionally related molecules, such as vascular, neuronal or chemokine receptors. Finally, autoantibodies targeting the endothelin receptor type A (EDNRA) exhibit chemotactic activity, as demonstrated by neutrophil migration toward HD-IgG in an EDNRA-dependent manner and in the direction of IgG from EDNRA-immunized mice. Our data characterizing the in vivo signatures of anti-GPCR autoantibodies thus suggest that they are a physiological part of the immune system.
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  • English
Open access status
gold
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https://sonar.ch/global/documents/278831
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