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

We provide evidence of a network of immunoglobulin G (IgG) autoantibodies targeting G protein-coupled receptors (GPCR) in sera from healthy donor (HD) individuals. A comparative analysis of autoantibody networks is also carried out in patients with systemic sclerosis, Alzheimer’s disease and ovarian cancer. The results indicate that sex, age and pathological conditions affect autoantibodies correlation and hierarchical clustering signatures, yet many of the correlations are shared across all groups, indicating alterations of homeostasis. Furthermore, we identify relationships between autoantibodies targeting structurally and functionally related molecules such as vascular, neuronal or chemokine receptors. Finally, autoantibodies targeting a GPCR, endothelin receptor type A (EDNRA), exhibit chemotactic activity as demonstrated in neutrophil migration toward HD-IgG in an EDNRA-dependent manner and in the direction of IgG from EDNRA-immunized mice