Identification of Antibodies to Chondrocyte and Synoviocyte Antigens in Equine Osteoarthritis

Innate immune responses within the joint are now known to play a key role in osteoarthritis (OA) pathogenesis. However, comparatively little is known regarding the role of adaptive immune responses in OA, and whether they may be important for initiating and sustaining progressive low-level joint inflammation. Therefore, we evaluated spontaneous osteoarthritis in horses to investigate whether antibodies recognizing live joint cells (chondrocytes, synoviocytes) were present in blood or synovial fluid, and to identify possible cellular target antigens. We found that horses with advanced OA had antibodies present in synovial fluid (SF) and plasma that recognized antigens expressed by chondrocytes and synoviocytes isolated from healthy joint tissues. Antibody concentrations correlated with clinical and arthroscopic scoring of OA severity. Antigenic targets for antibody recognition were expressed intracellularly and proteomic analysis of a prominent 60 kD protein band identified several proteins, including vimentin, calreticulin, and Hsp60, all of which are known to be antibody targets in patients with rheumatoid arthritis. Histological analysis of synovial biopsy samples from OA horses revealed the presence of numerous tertiary lymphoid structures with well-formed germinal centers, consistent with local antibody production within the joint synovium. Taken together, these studies in equine osteoarthritis revealed the presence of antibodies recognizing antigens expressed by live cells in the joint, which resembled similar immunologic processes recently described in rheumatoid arthritis. Broader questions raised by these findings include identification of triggers for local antibody production and new strategies to target this immune pathway in progressive OA.