Immune Reactivity to Connective Tissue Antigens in Pristane Induced Arthritis

OBJECTIVE: Pristane induced arthritis (PIA) is a seropositive experimental murine model that closely resembles rheumatoid arthritis (RA). Immune reactivity to a broad spectrum of autoantigens has been recognized in this disease model. We investigated the specificity of the autoimmune response in PIA to determine whether reactivity to connective tissue antigens is associated with the development of arthritis. METHODS: DBA/1 mice were injected with pristane and evaluated for development of joint disease and autoimmunity. Lymph nodes, spleen, sera, and arthritic paws were investigated at 1, 2, 4, 6, 9, and 12 months postinjection. T cell responses to 16 different joint components were evaluated using proliferation assays, and sera were assayed by ELISA for antibodies to these joint antigens. Cytokine concentrations after antigenic stimulation were assessed by ELISA in cultured cell supernatants and by real-time polymerase chain reaction using mRNA from spleens and arthritic paws. RESULTS: ELISA revealed positive responses to glucose-6-phosphate isomerase, chondroitin sulfate B, collagen I, collagen II, aggrecan, and DNA between 4 and 12 months post-pristane injection. In vitro tumor necrosis factor-a (TNF-a), interferon-g (IFN-g), and interleukin 6 (IL-6) responses were detected during reactions to most antigens tested, while IL-4 responses were absent. Cytokine analysis in arthritic joints revealed consistent expression of IL-1, IL-4, IL-6, TNF-a, and IFN-g mRNA. CONCLUSION: These results indicate that PIA animals develop both T cell and antibody responses to a broad spectrum of connective tissue antigens. Biglycan, aggrecan, and decorin may be relevant antigens in the pathogenesis of PIA, but no specific reaction pattern could be associated with the occurrence of disease. The data suggest that the development of pristane arthritis is not dependent upon reactivity against a single connective tissue antigen, but is a polyspecific autoimmune response to joint components elicited in pristane injected mice.