Immunization of rats with native bovine type I1 collagen results ih a polyarthritis by day 21 in approximately 40% of the rats. Sera of these rats contained anticollagen IgG, principally IgG2a. Small amounts of IgG2b were alsd detected, but IgGl and IgG2c were absent. By enzyme-linked immunosorbent assay, the paw tissue of these polyarthritic rats was shown to codtain anticollagen IgG, the principal subclass being IgG2a, with minor amounts of IgGZb. Immunofluorescence examination of the paws from polyarthritic rats demonstrated deposition of both IgG and C3 on the articular surface. Passive transfer of disease was accomplished by injection of affinity-purified anticollagen immunoglobulin into naive recipients; paw swelling and histopathologic changes were detected 24 hours after transfer, and by immunofluorescence techniques IgG and C3 deposits were demonstrable on the articular cartilage. On passive transfer, neutrophils invaded the joint space and became juxtaposed to the surface of the articular cartilage. Passive transfer of the disease with anticollagen immunoglobulin was unsuccessful after rats were decomplemented with cobra venom factor; immunofluorescence demonstrated IgG but not C3 on the articular cartilage of these decomplemented rats. In rats decomplemented with cobra venom factor, neutrophils did not accumulate in the joint and erosion of articular cartilage was not detected.Antibodies to collagen have been detected in the sera and synovial fluids of certain patients with rheumatoid arthritis (1-1 1) suggesting that autoimmunity to collagen may contribute, at least in part, to the disease process. Following these observations, studies by Trentham et a1 and others (12-20) have shown that immunization of rats with type I1 collagen results in an inflammatory polyarthritis in approximately 40% of the immunized animals. Collagen antibody titers in the sera of rats with polyarthritis were, in general, higher than in the sera of immunized but nonarthritic rats. Thus, like human rheumatoid arthritis, the polyarthritis in the collagen model may be related, at least in part, to collagen autoimmunity. Pathologic changes in the joints of rats with collagen-induced arthritis are similar to the acute phase of human rheumatoid arthritis: there is tenosynovitis, with polymorphonuclear leukocytes and mononuclear cells invading the joint space, and erosion of cartilage from the articular side with relative sparing of bone.Studies related to the mechanism of induction of polyarthritis by type I1 collagen have shown that the disease can be transferred passively by the administration of sensitized spleen and lymph node cells (21). Attempts to transfer the disease with serum from arthritic donors were initially unsuccessful (21), although this has recently been accomplished by Stuart et al (22). Additional studies related to the mechanism

Arthritic synovial tissue when cultured with normal articular cartilage induces a breakdown of articular cartilage proteoglycans. No collagen breakdown occurs unless the macroglobulins are inactivated by pretreatment with acid. Proteoglycan breakdown is most likely due to the continuous secretion of hydrolases by the synovium. A proteolytic enzyme has been found in the culture medium which has a pH optimum around 7.6, and is Ca++ dependent. Both indomethacin and hydrocortisone are inhibitors of proteoglycan breakdown.

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