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

Otavio Cabral-Marques, Alexandre Marques, Lasse Melvær Giil, Roberta De Vito, Judith Rademacher, Jeannine Günther, Tanja Lange, Jens Y. Humrich, Sebastian Klapa, Susanne Schinke, Lena F. Schimke, Gabriele Marschner, Silke Pitann, Sabine Adler, Ralf Dechend, Dominik N. Müller, Ioana Braicu, Jalid Sehouli, Kai Schulze-Forster, Tobias TrippelCarmen Scheibenbogen, Annetine Staff, Peter R. Mertens, Madlen Löbel, Justin Mastroianni, Corinna Plattfaut, Frank Gieseler, Duska Dragun, Barbara Engelhardt Martin, Maria J. Fernandez-Cabezudo, Hans D. Ochs, Basel K. al-Ramadi, Peter Lamprecht, Antje Mueller, Harald Heidecke, Gabriela Riemekasten

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number5224
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

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

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    Cabral-Marques, O., Marques, A., Giil, L. M., De Vito, R., Rademacher, J., Günther, J., Lange, T., Humrich, J. Y., Klapa, S., Schinke, S., Schimke, L. F., Marschner, G., Pitann, S., Adler, S., Dechend, R., Müller, D. N., Braicu, I., Sehouli, J., Schulze-Forster, K., ... Riemekasten, G. (2018). GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis. Nature communications, 9(1), [5224]. https://doi.org/10.1038/s41467-018-07598-9