Systemic and local autoantibody responses to extracellular matrix proteins define inflammatory phenotypes across...

Autoantibodies targeting extracellular matrix proteins are emerging as critical contributors to arthritis pathogenesis, yet their presence across different arthropathies remains incompletely characterized. This study investigated systemic and local expression of proteoglycan 4 (PRG4) and cartilage oligomeric matrix protein (COMP), alongside their corresponding autoantibodies, in healthy controls and patients with OA, RA or JIA.

Serum and SF samples were analysed by ELISA from control subjects, and OA, RA and JIA patients.

Serum PRG4 levels were significantly decreased in RA compared with controls and OA, while JIA patients showed elevated levels. Serum COMP was significantly elevated in OA and JIA compared with controls and RA. In SF, OA showed decreased PRG4 compared with all other groups, while COMP levels were highest in OA and controls. Anti-PRG4 autoantibodies were significantly elevated in all disease groups compared with controls in serum, with RA and JIA also showing increased elevation in SF. Anti-COMP autoantibodies were significantly increased in RA and JIA serum and elevated in all disease groups in SF compared with controls. Notably, a positive correlation between PRG4 protein and anti-PRG4 antibodies was observed specifically in OA SF, suggesting local antigen-driven immune responses.

These findings demonstrate that autoantibodies against PRG4 and COMP are present across arthropathies with distinct patterns reflecting different pathogenic mechanisms. The detection of these autoantibodies provides mechanistic insights into disease progression and potential biomarkers for identifying differential pathway activation/inflammatory subgroups within arthropathies.