Proteoglycan-induced arthritis: immune regulation, cellular mechanisms, and genetics

Rheumatoid arthritis is probably the least understood systemic autoimmune disease, and it affects approximately 1% of the human population. Several lines of evidence indicate that the effector mechanism, which initially attacks small joints, is T-cell driven. As a result, an aggressive synovial pannus develops, which destroys articular cartilage and bone, leading to massive ankylosis and deformities of peripheral joints. The disease has a progressive character, with the involvement of more and more joints. Although the target organ is the synovial joint, there is no clear evidence that any macromolecule of cartilaginous tissues, bone, or synovium, could be a preferential autoantigen. There are numerous rodent models that simulate some or many of the clinical, immunological, or histopathological features of the disease. Recently, it has become a strong working hypothesis that MHC and non-MHC genetic components share loci that are common in various autoimmune diseases, and in corresponding animal models. The most relevant animal models of rheumatoid arthritis appear to be those induced by cartilage matrix components such as type II collagen or proteoglycan aggrecan. This review summarizes our current knowledge of cartilage proteoglycan (aggrecan)-induced arthritis in mice.