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

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Item Type:Article
Title:GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis
Creators Name:Cabral-Marques, O. and Marques, A. and Giil, L.M. and De Vito, R. and Rademacher, J. and Günther, J. and Lange, T. and Humrich, J.Y. and Klapa, S. and Schinke, S. and Schimke, L.F. and Marschner, G. and Pitann, S. and Adler, S. and Dechend, R. and Müller, D.N. and Braicu, I. and Sehouli, J. and Schulze-Forster, K. and Trippel, T. and Scheibenbogen, C. and Staff, A. and Mertens, P.R. and Löbel, M. and Mastroianni, J. and Plattfaut, C. and Gieseler, F. and Dragun, D. and Engelhardt, B.E. and Fernandez-Cabezudo, M.J. and Ochs, H.D. and Al-Ramadi, B.K. and Lamprecht, P. and Mueller, A. and Heidecke, H. and Riemekasten, G.
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.
Keywords:Alzheimer Disease, Amino Acid Sequence, Amino Acid Sequence Homology, Autoantibodies, Endothelin A Receptor, G-Protein-Coupled Receptors, Homeostasis, Immunoglobulin G, Ovarian Neoplasms, Protein Interaction Maps, Systemic Scleroderma, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:9
Number:1
Page Range:5224
Date:6 December 2018
Official Publication:https://doi.org/10.1038/s41467-018-07598-9
PubMed:View item in PubMed

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