Immunization of Rats with Homologous Type XI Collagen Leads to Chronic and Relapsing Arthritis with Different Genetics and Joint Pathology Than Arthritis Induced with Homologous Type II Collagen

Abstract

The most commonly used animal model for rheumatoid arthritis (RA) is collagen-induced arthritis (CIA), induced by immunization with type II collagen (CII), a cartilage restricted protein. In this work we show that type XI collagen (CXI), which is a minor component in cartilage, induces a different form of erosive and chronic relapsing polyarthritis in rats. Using a series of inbred rat strains involving various genetic backgrounds (DA, LEW, E3), and congenic MHC regions (a, u, f, n, c, d), we found that CXI induced arthritis (CXIIA) is associated with the RT1f haplotype in contrast to CII induced arthritis (CIIIA), which is associated with the RT1a and RT1u haplotypes. The CXIIA follows a chronic disease course affecting peripheral joints with both progression and relapses, which appear not to cease (occurring >800 days). Susceptible strains showed a sustained antibody response to CXI with time indicating that the autoimmune response was self-perpetuated. Microscopic analysis of the joints at different stages demonstrated the severe destruction of bone and cartilage by pannus tissue consisting of activated macrophages and T cells. The main difference to joints from rats with CIIIA was larger numbers of infiltrating lymphocytes and these tended to form follicle-like aggregates. Surprisingly, males were more susceptible to CXIIA than females whereas the opposite has been observed in other rat arthritis models, including CIIIA. Taken together, CXIIA is a chronic relapsing and erosive polyarthritis that is MHC associated, which in fact fulfills the criteria for diagnosis of RA. Thus the CXIIA model will be useful as a novel and relevant animal model for RA.