The role of HLA-B27 in spondyloarthritis

The human major histocompatibility complex (MHC) class I allele HLA-B27 bea rs a striking association with the spondylolarthritic group of inflammatory arthritides, yet despite extensive studies its role in the disease process remains obscure. As an MHC class I protein, the primary function of HLA-B2 7 is to complex with beta(2)-microglobulin forming a structure that present s short antigenic peptides for recognition by cytotoxic T lymphocytes (CTL) . It has been proposed that the role of HLA-B27 in spondyloarthropathy invo lves this process of antigen presentation, and of the numerous theories pro posed to explain the association, the most popular have involved the bindin g and presentation of "arthritogenic" peptides. Transgenic rodent studies d irectly implicate HLA-B27 heavy chains in disease pathogenesis, but suggest that the mechanism may be distinct from their primary function. The recent demonstration that HLA-B27 heavy chains can form stable homodimers may thu s be of relevance. This review summarizes the evidence supporting current t heories of disease association and proposes an alternative model of disease based on recent findings.