Ankylosing Spondylitis Pathogenesis and Pathophysiology

The pathogenesis and pathophysiology of Ankylosing Spondylitis (AS) is complex and remains only partially understood. Contributory genes including a variety of HLA-B27 subset genes and many other non-HLA genes are implicated in the literature. Novel genes and gene–gene interactions being a continuously evolving area of AS research. Dysregulation of the enteric microbiome with a corresponding aberrant immunological response is recognised in research. Certain infectious agents are thought to play a role. A variety of other influences including environmental exposures, dietary and lifestyle factors and sex hormones appear to play a role in AS pathogenesis. There is emerging evidence that that pathophysiological response in AS is an elaborate combination of both autoinflammatory and autoimmune components, however the IL-17/IL-23 pathway remains the major pathway in AS according to studies to date. The specific mechanisms that lead to characteristic clinical features of AS including sacroiliitis, spondylitis, ankylosis, uveitis and other extra articular manifestations remain occult. Further research to establish these is ongoing.