Type Ii Collagen - Induced Arthritis in Mice

The induction of immunological reactivity to type II collagen, a major component of cartilage, has recently been used to establish an experimental model of arthritis in the rat (1). Trentham and colleagues (1) have shown that the intradermal injection of collagen in Freund's complete or incomplete adjuvant elicits an arthritogenic reaction, specifically with native type II collagen. Arthritis occurs in 40% of the rats injected, and this arthritis could be passively transferred by the transplantation of immunocompetent cells (2). There was also a correlation between the humoral response to type II collagen and the occurrence of arthritis (3). The relationship between the collagen arthritis model in the rat and rheumatoid arthritis (RA) 1 is unclear. The histology demonstrated in the experimental model (I) was very similar to that seen in RA, and x-rays taken of the joints of affected rats show erosive damage as seen in human rheumatoid disease (4). Autoimmunity to type II collagen has been observed in RA, with circulating antibodies in the majority of patients (5, 6) and an abnormal cellular response assessed by leukocyte inhibition factor production (7). It is conceivable that an abnormal immune response to type II collagen could be relevant in the joint inflammation found in RA. It has been shown that antigens of the major histocompatibility complex (MHC) may be related to both the susceptibility to disease (8, 9) and the control of the immune response (10, 11). Because human lymphocyte antigens influence susceptibility to various human arthritides, it is particularly relevant to examine the genetic control of the immune response to type II collagen in the experimental model of arthritis. However, the M H C of rats is not as well documented as that of mice. Recent evidence has shown that type II collagen arthritis may be induced in mice (12). This paper reports on the incidence of type II collagen arthritis in various strains of mice and maps the susceptibility to the disease within the I region of the MHC. The humoral immune response to type II collagen was also investigated, and strains susceptible to type II collagen arthritis correlate well with high antibody responders to the same antigen.