Cartilage oligomeric matrix protein (COMP)-induced arthritis in rats

In rheumatoid arthritis peripheral cartilaginous joints are inflamed and er oded. One driving factor may be an immune response towards proteins in the cartilage. Here it is shown that cartilage oligomeric matrix protein (COMP) , expressed specifically in cartilage, is arthritogenic in the rat. Both na tive and denatured rat COMP induced severe arthritis in selected rat strain s. The arthritis occurred only in peripheral joints which were attacked by an erosive inflammatory process similar to that seen in the human disease. The disease was self-limited and no permanent destruction of joints was see n macroscopically. Disease development appeared to be dependent on an immun e response to autologous (rat) COMP and not on cross-reactivity to other ca rtilage rat collagens (types II, IX and XI). The disease and the immune res ponse to COMP were genetically controlled by the MHC; the RT1(u) and RT1(1) haplotypes were more susceptible than the a, c, d, f and n haplotypes. Bot h LEW and E3 gene backgrounds were highly permissive for disease induction. These findings suggest that the induction of arthritis with rat COMP repre sents a unique pathogenesis which is controlled by different genes compared with collagen-induced arthritis or adjuvant-induced arthritis.