COLLAGEN-INDUCED ARTHRITIS, AN ANIMAL-MODEL OF AUTOIMMUNITY

Collagen induced arthritis (CIA) is an autoimmune model that in many w ays resembles rheumatoid arthritis (RA). Immunization of genetically s usceptible strains of rodents and primates with type II collagen (CII) leads to the development of a severe polyarticular arthritis that is mediated by an autoimmune response. Like RA, synovitis and erosions of cartilage and bone are hallmarks of CIA, and susceptibility to both R A and CIA is linked to the expression of specific MHC class II molecul es. Although not identical to RA, CIA clearly establishes the biologic al plausibility that an autoimmune reaction to a cartilage component c an lead to a chronic, destructive, polyarthritis. Although it is induc ed in susceptible animals by immunization with heterologous CII, it is the autoreactive component of the immune response that leads to disea se. A wealth of evidence indicates that synovitis is initiated by the production of pathogenic autoreactive antibodies capable of fixing and activating complement. The elucidation of the specific amino acid seq uences of collagen that are recognized by the MHC molecules has enable d at least two approaches to specific immunotherapy to be considered. Firstly, small synthetic peptides representing dominant epitopes have been used as effectively as the original antigen as a tolerogen. The r ather fastidious physicochemical properties of collagen that make it d ifficult for its routine use in therapy are thereby circumvented by th e use of oligopeptides. Secondly, analysis of the specific amino acid side chains that are involved in MHC contact and TCR recognition enabl es analog peptides to be devised which can specifically and exquisitel y inhibit the response to CII, preventing the onset of arthritis. Furt her investigations involving this model may contribute to the developm ent of specific immunotherapies in the human disorder.