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

Otavio Cabral-Marques (), Alexandre Marques, Lasse Melvær Giil, Roberta 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 Trippel, Carmen Scheibenbogen, Annetine Staff, Peter R. Mertens, Madlen Löbel, Justin Mastroianni, Corinna Plattfaut, Frank Gieseler, Duska Dragun, Barbara Elizabeth Engelhardt, Maria J. Fernandez-Cabezudo, Hans D. Ochs, Basel K. al-Ramadi, Peter Lamprecht, Antje Mueller, Harald Heidecke and Gabriela Riemekasten ()
Additional contact information
Otavio Cabral-Marques: University of Lübeck
Alexandre Marques: University of Lübeck
Lasse Melvær Giil: University of Bergen
Roberta Vito: Princeton University
Judith Rademacher: Charité University Hospital
Jeannine Günther: Charité University Hospital
Tanja Lange: University of Lübeck
Jens Y. Humrich: University of Lübeck
Sebastian Klapa: University of Lübeck
Susanne Schinke: University of Lübeck
Lena F. Schimke: University of Lübeck
Gabriele Marschner: University of Lübeck
Silke Pitann: University of Lübeck
Sabine Adler: University Hospital and University of Bern
Ralf Dechend: Experimental and Clinical Research Center, a collaboration of Max Delbruck Center for Molecular Medicine and Charité Universitätsmedizin
Dominik N. Müller: Experimental and Clinical Research Center, a collaboration of Max Delbruck Center for Molecular Medicine and Charité Universitätsmedizin
Ioana Braicu: Charité University Hospital
Jalid Sehouli: Charité University Hospital, Berlin and Tumor Bank Ovarian Cancer Network (TOC)
Kai Schulze-Forster: Charité University Hospital
Tobias Trippel: Charité University Hospital
Carmen Scheibenbogen: Charité University Hospital Berlin
Annetine Staff: University of Oslo and Oslo University Hospital
Peter R. Mertens: Otto-von-Guericke University Magdeburg
Madlen Löbel: Charité University Hospital Berlin
Justin Mastroianni: Albert Ludwigs University (ALU) of Freiburg
Corinna Plattfaut: University of Lübeck
Frank Gieseler: University of Lübeck
Duska Dragun: Charité University Hospital
Barbara Elizabeth Engelhardt: Princeton University
Maria J. Fernandez-Cabezudo: UAE University
Hans D. Ochs: Seattle Children’s Research Institute
Basel K. al-Ramadi: UAE University
Peter Lamprecht: University of Lübeck
Antje Mueller: University of Lübeck
Harald Heidecke: Charité University Hospital
Gabriela Riemekasten: University of Lübeck

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07598-9

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DOI: 10.1038/s41467-018-07598-9

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