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, Barbara Elizabeth
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
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
U2 - 10.1038/s41467-018-07598-9
DO - 10.1038/s41467-018-07598-9
M3 - Journal articles
C2 - 30523250
AN - SCOPUS:85058026814
SN - 1751-8628
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5224
ER -
