Why HLA-B27: an analysis based on two animal models

The histocompatibility antigen HLA-B27 predisposes to at least three diseases: ankylosing spondylitis, Reiter's syndrome, and acute anterior uveitis. Despite its marked association with these diseases, the mechanism of the predisposition remains speculative. Two animal models, those of adjuvant arthritis and endotoxin-induced uveitis, are particularly relevant to an understanding of B27-related disease. An analysis of these two models is useful in considering hypotheses on the mechanism of the B27-related predisposition. The proposal that HLA-B27 itself or a gene closely linked to it confers an enhanced sensitivity to an inflammatory mediator such as a prostaglandin fits both with the animal models and observations on human disease. Studies to test this hypothesis are in progress.