Serum Transfer of Collagen - Induced Arthritis

In 1977, Trentham et al. (1) described a model of polyarthritis induced in rats by immunization with type II collagen. The lesions identified on histopathologic examination resembled those of human rheumatoid arthritis (RA) 1. In addition, the arthritis was associated with high levels of both cellular and humoral immunity to collagen (2). Since collagen-related autoimmunity has also been described in individuals with RA (3-6), Trentham proposed that the same pathophysiologic mechanism responsible for collagen-induced arthritis in rats might cause some of the lesions in RA (7). Type II collagen is limited in its bodily distribution primarily to cartilage (8), so an immune response to this specific collagen could account for the predilection of RA to involve diarthroidal joints. However, the earliest lesion of collagen-induced arthritis is synovial proliferation in the absence of apparent cartilage abnormality. To determine the precise sequence of events leading to experimental arthritis, detailed investigations of the immune response to type II collagen in rats were undertaken. Kinetic studies showed rising levels of both cellular and humoral immunity to collagen at the time arthritis appeared (9). Apparently, the disease could be transferred with either cells (10) or with an immunoglobulin concentrate (11) from collagen-immunized donors. In addition to rats, some mice were susceptible to collagen-induced arthritis (12) but, according to one report (13), only strains of the H-2 q major histocompatibility haplotype. In humans, the major histocompatibility haplotype HLADR4 is also associated with immune responsiveness to collagen (14) and with RA (15), providing additional evidence that collagen-induced arthritis is a relevant model for the study of RA. Unfortunately, no simple correlation is obvious between the immune response to collagen and collagen-induced arthritis in mice. Although strains that are susceptible to arthritis have concomitantly high anticollagen responses, many resistant strains have equally high responses. Either the immune response to collagen is qualitatively different in the latter stains, or other factors in the host milieu are independent determinants of susceptibility to arthritis. The present studies were undertaken to determine if arthritis could be trans-