The role of HLA-B*27 in spondyloarthritis

Abstract

The mechanism by which HLA-B*27 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-B*27 can activate the IL-23/IL-17 axis in HLA-B*27 transgenic rats and humans. In HLA-B*27-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-B*27 to the disease and provide a potential explanation for HLA-B*27-negative spondyloarthritis. Gut microbial dysbiosis may be important in the development of spondyloarthritis. HLA-B*27-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-B*27 in disease requires further investigation, considerable progress has been made in understanding this complex relationship.

Keywords: Ankylosing spondylitis; Arthritogenic peptides; Autophagy; Dysbiosis; Endoplasmic reticulum-associated aminopeptidase-1 (ERAP1); Endoplasmic reticulum-associated degradation (ERAD); Inflammatory bowel disease; Microbiota; Protein misfolding; Spondyloarthritis.