Experimental autoimmune arthritis in mice. I. Homologous type II collagen is responsible for self-perpetuating...

Immunisation with heterologous type II collagen (CII) induces arthritis in mice of the DBA/1 strain, which is genetically susceptible to this disease. To develop an experimental model of autoimmunity more adequate for the study of human rheumatoid arthritis (RA), DBA/1 mice were injected with 100 micrograms of native CII that had been purified from mouse xiphoid cartilage. About six weeks later the animals developed a chronic progressive polyarthritis involving the four paws but mainly confined to interphalangeal and metatarsophalangeal joints. The evolution of the disease fluctuated between remissions and exacerbations. The initial lesions assessed by clinical observations were more severe when the disease occurred early than in the case of late onset. Interestingly, the incidence of arthritis was clearly preponderant in males, and, moreover, the few female mice which developed arthritis had mild disease states with lower arthritic scores than the males. Varying levels of autoantibodies against mouse CII were found in the sera of immunised animals, regardless of the development of arthritis. These data indicate that the injection of homologous CII into mice caused a polyarthritis that is clinically closer to the human RA than the disease induced with heterologous CII and therefore will represent a useful tool for the study of the self-perpetuating mechanisms that characterise RA.