Autoantibodies directed against specific G-protein coupled receptors (GPCR) have been identified to display prognostic and functional relevance in patients with systemic sclerosis (SSc), a chronic-inflammatory autoimmune disease. Recently, it has been demonstrated that IgG derived from SSc patients exhibit a disease-specific pattern of anti-GPCR autoantibodies. In addition, PBMC express various GPCR and show disease-specific alterations in their GPCR expression pattern in SSc. IgG fractions derived from SSc patients were able to induce high concentrations of interleukin-8 in supernatants of PBMC compared to IgG fractions from healthy donors, indicating a role of anti-GPCR-autoantibody-induced GPCR stimulation on the release of cytokines. It is known that patients with rheumatic diseases often show alterations in the cytokine profile compared to healthy controls. Based on anti-GPCR-autoantibody-induced cytokine expression and assuming a causal role of anti-GPCR autoantibodies in disease mechanisms in other rheumatic diseases as well, we hypothesize a stimulating and disease-specific effect of anti-GPCR autoantibodies on cytokine release of PBMC. 

In this project, we want to investigate if interactions between GPCR, especially AT1R, ETAR, CXCR3, CXCR4, CaSR, b-ADR and PAR-2, and their specific autoantibodies modulate the cytokine profile in patients with SSc, rheumatoid arthritis, and giant cell arteritis. In particular, we want to find out if anti-GPCR IgG autoantibodies are able to induce the release of pro-inflammatory cytokines (TNFa, IL-6 and IL-17A) from PBMC of healthy donors in a disease-specific way.