Fetuin-A and calciprotein particles in rheumatoid arthritis

• Applicant: Professor Dr. Ulf Wagner
• Subject Area: Rheumatology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 557726607

Calciprotein particles (CPP) are part of the physiological calcium homeostasis. However, in monocytes from RA patients, increased CPP concentrations in the presence of sufficient Ca2+ concentrations trigger pathological NLRP3 inflammasome activation and massive IL-1β release. Determination of the concentration of calciprotein particles in sera from patients with rheumatoid arthritis showed an association with various clinical parameters, including the erosiveness of the disease and the clinical disease activity indices DAS28 and CDAI. In addition to calciprotein particles, membrane-containing calcium phosphate particles also showed a very stringent correlation with disease activity. The most important protein component of CPP is fetuin-A, which binds Ca2+ and phosphate and prevents crystallization. In RA patients, the fetuin-A concentration is significantly reduced compared to healthy controls. The proposed project aims to elucidate the exact role of CPP in inflammation and bone erosion in arthritis. In preliminary work, the concentration of CPP has already been correlated with the occurrence of collagen-induced arthritis. In human studies, we will investigate the ionic and protein composition of CPPs isolated from the serum and synovial fluid of RA patients and compare them with healthy individuals and disease controls. The aim is to distinguish between pro-inflammatory, RA-related CPPs and anti-inflammatory CPPs and to determine their characteristic composition and properties. The results will also be used to develop therapeutic strategies. Based on the results, we will investigate potential therapeutic approaches in RA aimed at modulating CPP composition and concentration. In selected animal experiments, possibilities of therapeutically influencing the final pathway of joint destruction by exogenous fetuin A and phosphate binders will be investigated. In a clinical study, CPP will be evaluated as an indicator for the clinical course and tested as a prognostic indicator for the response to various biological DMARDS. Our long-term goal is to develop a diagnostic assay and to identify potential therapeutic approaches in RA with agents already tested for use in humans, such as phosphate binders.

• DFG Programme: Research Grants