Immunogenicity of recombinant type IX collagen in murine collagen-induced arthritis

Objective. Past attempts to isolate type IX collagen (CIX) from cartilage using limited proteolysis yielded partially degraded material. Recent application of recombinant technology, however, has allowed the preparation of intact native CIX. We used the murine collagen-induced arthritis model to characterize the immunologic properties of recombinant human CIX (rCIX) produced using a baculovirus expression system. Methods. A panel of B10 congenic mice was immunized with rCIX emulsified with Freund's complete adjuvant (CFA). The ability of the rCIX to induce tolerance and suppress arthritis was determined by administration intravenously or orally before challenge with CII/CFA. Results. None of the mice immunized with rCIX developed overt arthritis, although 2 of 5 HLA-DR1 transgenic mice developed limited digital erythema and swelling. Recombinant CIX administered by either route effectively induced suppression of arthritis, although the suppression was less pronounced than that induced with CII Immune responses to CIX and CII were specific, suggesting that bystander suppression, rather than cross-reactivity with CII, was instrumental in suppressing arthritis. Conclusion. These data show that CIX down-regulates arthritis in mice while having no associated risk of inducing arthritis.