Immunogenetics of collagen induced arthritis in mice: a model for human polyarthritis

Abstract

Collagen induced arthritis is an experimental animal model of inflammatory polyarthropathy that has many features of human rheumatoid arthritis. Type II collagen is the major matrix protein of hyaline cartilage and is a sequestered protein which can be presented as an autoantigen under certain conditions. To induce CIA, type II collagen is injected intradermally with complete Freund's adjuvant. Susceptibility to CIA is dependent on the presence of the trimolecular complex: 1) the arthritogenic epitope on the type II collagen; 2) a class II MHC molecule on the accessory cell presenting the arthritogenic epitope; and 3) T cells expressing specific V beta chains in their TCRs. Complement and other non-MHC background genes also may play a role in susceptibility to CIA. Both cell mediated and humoral immunity are involved in the pathogenesis of CIA. To date immunotherapies that have modulated CIA include use of anti-class Ii antibodies, anti-lymphokines, and monoclonal antibodies directed against specific cellular markers. All of these therapies are able to modulate disease to some extent but lack the specificity and efficacy to make them practical for widespread use in human disease. Most promising, is the use of monoclonal antibodies directed against specific V beta TCR subsets. This is potentially a very specific and effective therapy because it will affect only the cells involved in disease while leaving the host otherwise immunocompetent. Therapies on the horizon include the use of synthetic peptides with sequences homologous to various regions on the TCR, immunotoxins, and superantigens to modulate the immune response and ameliorate disease.(ABSTRACT TRUNCATED AT 250 WORDS)