The role of HLA-B*27 in spondyloarthritis.

The mechanism by which HLA-B27 predisposes to spondyloarthritis remains unresolved. Arthritogenic peptides have not been defined in humans and are not involved in experimental models of spondyloarthritis. Aberrant properties of HLA-B27 can activate the IL-23/IL-17 axis in HLA-B27 transgenic rats and humans. In HLA-B27-independent rodent models, spondyloarthritis can be driven by IL-23 triggering entheseal-resident CD4/CD8 T cells or CD4 Th17 T cells. These findings point toward noncanonical mechanisms linking HLA-B27 to the disease and provide a potential explanation for HLA-B27-negative spondyloarthritis. Gut microbial dysbiosis may be important in the development of spondyloarthritis. HLA-B27-induced changes in gut microbiota are complex and suggest an ecological model of dysbiosis in rodents. The importance of the IL-23/IL-17 axis in ankylosing spondylitis has been demonstrated by studies showing efficacy of IL-17. Although deciphering the precise role(s) of HLA-B27 in disease requires further investigation, considerable progress has been made in understanding this complex relationship.