CHRONIC CRYSTAL-INDUCED ARTHRITIS

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Chronic arthritis is a multifactorial event that involves both immune and nonimmune biologic systems. This is a pilot project to test the hypotheses that 1) genetic variation in the "non-immune" components of inflammatory joint disease exist, and 2) that this inherited variability contributes significantly to the wide spectrum of disease incidence and severity that is displayed by elderly patients with osteoarthritis and other non-rheumatoid joint diseases. None of the existing animal models of osteoarthritis are suitable for genetic evaluation. A model of chronic crystal-induced arthritis (CCIA) in rats (LEW, DA strains) will be established by repeated (weekly) intra-articular injections of sodium urate, calcium urate, or calcium pyrophosphate crystals. The model will be characterized on the basis of clinical and histological evaluations of progression from the acute (single injection) to the chronic (5-8 injections) stages of joint inflammation. Experimental variables such as dose-response, sex and age (1-9 months) of the test rats will be assessed for importance. Selected (15) inbred rat strains will be tested for susceptibility to CCIA by the optimum protocol as determined initially. Test strains include prototype and inbred-congenic strains available through NIH or our own rat colony at the University of Utah. Strain-specific differences in either the acute or chronic phases of CCIA will be sought on the basis of severity or ease of induction. To determine if auto-antibody to cartilage collagen develops secondary to chronic arthritis, serum and joint eluates (dilute acetic acid) from rats with CCIA will be assayed for IgG and IgM anti-type II collagen antibodies by ELISA. This is important, as genetic variation in degree of immune response to collagen is known and must be either identified as an aggravating component of CCIA severity or eliminated as an overriding genetic variant in these studies.