Collagen induced arthritis (CIA)is an animal model that in many ways resembles rheumatoid arthritis (RA). CIA can be induced in susceptible animals by immunization with type II collagen (CII). Like RA,CIA is characterized by intense joint inflammation and destruction.On histological examination,there is synovitis accompanied by erosion of cartilage and subchondral bone. Autoanti-bodies to CII initiate joint inflammation by binding to articular cartilage,forming antigen-antibody complexes locally and activating hemolytic complement. Susceptibility to CIA in mice is linked to the expression of specific class II MHC Molecules,which dictate the T cell determinants on CII,and therefore,the subsets of T cells that can be activated by CII.In addition to activation of B cells reactive to CII,the T cells stimulate monocytes/macrophages.These cells amplify the inflammatory cascade by secretion of proinflammatory monokines, including TNF-alpha and IL-1,leading to the production of other proinflammatory proteins,including matrix metalloproteinases (MMPs).The importance of CIA lies in its possible relationship to arthritis in humans.Progress in understanding CIA has contributed to the development of new therapies for RA.In addition,it has been found that mice with human HLA-DR1,DR4 and HLA-DQ8 transgenes,which have been demonstrated to be the susceptibility markers for RA, confer susceptibility to CIA.These observations coupled with the finding of T cells and B cells reactive with CII in the inflamed joints of RA patients establish the potential role of CII autoimmunity in the pathogenesis of RA.
Animals ; Antigen-Antibody Complex ; Arthritis ; Arthritis, Experimental* ; Arthritis, Rheumatoid* ; Autoimmunity* ; B-Lymphocytes ; Cartilage ; Collagen ; Collagen Type II* ; Complement System Proteins ; Humans ; Immunization ; Inflammation ; Joints ; Matrix Metalloproteinases ; Mice ; Models, Animal ; Monokines ; Synovitis ; T-Lymphocytes ; Tumor Necrosis Factor-alpha