Homologous type II collagen induces chronic and progressive arthritis in mice

Abstract

Native mouse type I1 collagen was used for immunization of DBA/l mice. Arthritis developed exclusively in male animals and was characterized by a variable and delayed onset, a slow and progressive devebpment, and frequent exacerbations of disease in several joints including those that were previously affected. Titers of anti-type I1 collagen autoantibodies were found not to correlate well with arthritis development. It appears that experimental arthritis induced with homologous type I1 collagen resembles rheumatoid arthritis in humans, both in certain clinical features and in the lack of correspondence between anti-type I1 collagen autoantibody titers and disease symptoms.Type I1 collagen-induced arthritis provides an experimental model for autoimmune polyarthritis , originally introduced by Trentham et a1 in rats (1) and by Courtenay et a1 in mice (2). In rats, both homologous and heterologous type 11 collagen have been used for induction of arthritis (l), but in mice, only heterologous lype I1 collagen has been used (2). In both rats and mice, the disease course is characterized by a severe, acute phase, with no later exacerbations of disease (3). High titers of antibody against heterologous type 11 collagen have been seen preferentially in arthritic animals, suggesting that levels of anti-type I1 collagen antibodies may be critical for the development of the disease (4). Also, the successful induction of arthritis with immunoglobulin fractions from diseased animals has provided arguments for an important and perhaps necessary role of anti-type I1 collagen antibodies in collagen arthritis (5).The relevance of type I1 collagen-induced arthritis in rodents as a model for human rheumatoid arthritis has been a matter of debate. Both the lack of a relapsing character in collagen-induced arthritis and the lack of circulating anti-type I1 collagen antibodies in most humans with rheumatoid arthritis have been used to emphasize the dissimilarities between the respective conditions (see ref.3). It is not certain, however, that immunization with heterologous collagens, the method that has thus far been used in animal studies, provides the best model for a hypothetical autoimmunization against collagen in humans. It is possible that immunization of animals with homologous collagen could be more useful in this respect.Therefore, in the present study, we investigated the arthritis that can be induced in DBAl1 mice after immunization with homologous collagen. We characterized a large group of immunized animals as to clinical course and mean antibody titers against the immunogen, and in addition, we analyzed the disease course, the development of anti-type I1 collagen autoantibodies, and the final histopathologic picture in 10 male and 9 female DBAI1 mice. It is demonstrated that arthritis induced with mouse collagen is progressive and proceeds with an intermittent course. It is

Characterization of a spontaneously occurring arthritis in male DBA/1 mice

“…The first is that this disease shows several similarities to human rheumatoid arthritis in that it 'is chronic and remitting, and results in a joint destruction characterized by erosions that begin at the cartilage-synovial junction. These features, as well as the histopathologic findings in affected joints, are also shared by a few rodent models of induced arthritis, mainly those induced by the injection of homologous type 11 collagen into mice (9) and rats (11). Most other models of induced arthritis are only monophasic, not chronic.…”

“…Of special interest is the relationship between the spontaneous arthritis and the arthritis induced in DBAA mice with homologous collagen, considering the similarities in clinical course and macroscopic as well as microscopic appearance (9). Several possibilities exist.…”

“…The clinicid severity of arthritis in each foot was quantified on a scale of 1-3 (maximum score 12 for each animal). This grading system has been previously described (9) and used to evaluate collagen-induced arthritis.…”

Specificity of antibodies to type II collagen in rheumatoid arthritis

“…Four of 12 RA sera that were passed through an HI1 column did not contain species-specific antibodies (Table 3). Autologous type I1 collagen is itself immunogenic and is capable of inducing arthritis in mice (36), rats (I), and cynomolgus monkeys (unpublished observations).…”

“…It would appear that most RA pa-tients have antibodies similar to those that are generated in animals immunized with heterologous type I1 collagen. Antibodies produced in arthritis-susceptible animals react not only with the collagen used for immunization, but also with common antigenic determinants found on homologous type I1 collagens (10)(11)(12)15,36,37).…”