HLA-B27 transgenic mice are susceptible to collagen-induced arthritis: Type II collagen as a potential target in human disease

HLA-D27 is highly linked with a group of human diseases called spondyloarth ropathies (SpA). Many of these disorders begin after an infection with an e nterobacteria. The symptoms seen in patients with spondyloarthropathies are inflammatory pain in the spine and asymmetrical arthritis of lower limbs. Additional symptoms related to SpA include inflammation in the eyes, bowel, and skin. The autoantigen(s) in SpA are nor known. Proteins such as collag en and proteoglycans have been thought to be potent autoantigens in arthrit idis including B27-associated human diseases. Type II collagen Is a common denominator among eyes and joints, affected tissues in B27-linked diseases. Moreover, a few reports indicated CII specific T cells and antibodies in p atients with spondyloarthropathies. We and others have previously described development of spontaneous arthritis and nail disease in HLA-B27 transgeni c animals. To determine whether CII may be a target antigen in the B27-link ed diseases, B27 + m beta(2)m% (HLA-B27 transgenic mice lacking mouse beta( 2)m with and without human beta(2)m) mice were immunized with type II colla gen inside the barrier facility. Male HLA-B27 transgenic mice developed col lagen-induced arthritis compared to transgene negative littermates or femal e counterparts. There was no difference in the incidence of arthritis in HL A-B27 transgenic mice with and without human beta(2)m Our data suggest that beta(2)m free heavy chain of HLA-B27 may present soluble antigens such as type II collagen to trigger specific T cells contributing in the developmen t of arthritis. Our data also suggest that CII may be a potential target an tigen in the cartilage during the disease process. Human Immunology 61, 140 -147 (2000). (C) American Society for Histocompatibility and Immunogenetics , 2000. Published by Elsevier Science Inc.