TY - JOUR
T1 - GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis
AU - Cabral-Marques, Otavio
AU - Marques, Alexandre
AU - Giil, Lasse Melvær
AU - De Vito, Roberta
AU - Rademacher, Judith
AU - Günther, Jeannine
AU - Lange, Tanja
AU - Humrich, Jens Y.
AU - Klapa, Sebastian
AU - Schinke, Susanne
AU - Schimke, Lena F.
AU - Marschner, Gabriele
AU - Pitann, Silke
AU - Adler, Sabine
AU - Dechend, Ralf
AU - Müller, Dominik N.
AU - Braicu, Ioana
AU - Sehouli, Jalid
AU - Schulze-Forster, Kai
AU - Trippel, Tobias
AU - Scheibenbogen, Carmen
AU - Staff, Annetine
AU - Mertens, Peter R.
AU - Löbel, Madlen
AU - Mastroianni, Justin
AU - Plattfaut, Corinna
AU - Gieseler, Frank
AU - Dragun, Duska
AU - Engelhardt Martin, Barbara
AU - Fernandez-Cabezudo, Maria J.
AU - Ochs, Hans D.
AU - al-Ramadi, Basel K.
AU - Lamprecht, Peter
AU - Mueller, Antje
AU - Heidecke, Harald
AU - Riemekasten, Gabriela
N1 - Funding Information:
We thank all patients and HD for their participation in this study. We acknowledge Prof. Xinhua Yu and Prof. Frank Petersen from the Research Center Borstel, Airway Research Center North (ARCN), and Members of the German Center for Lung Research (DZL), Borstel, Germany, for providing sera from EDNRA-immunized and non-immunized mice. We thank the Mirjam Lichy Foundation for their support as well as the DFG (grant no. RI 1056-11/12) for financial support. We also thank Actelion Pharmaceutical GmbH, the Eppenauer/Gutzeit Foundation, the German Network of Systemic Sclerosis and the EUSTAR network for their support. This study was supported by the Charité University Hospital in Berlin and University Hospital of Schleswig-Holstein, Campus Lübeck.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85058026814&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058026814&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-07598-9
DO - 10.1038/s41467-018-07598-9
M3 - Article
C2 - 30523250
AN - SCOPUS:85058026814
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5224
ER -