Anatomic and genetic considerations in the pathogenesis of ankylosing spondylitis

Investigations have focused on the association between ankylosing spondylitis and HLA-B27; several theories have been offered, including linkage disequilibrium, molecular mimicry involving either autoimmunity or tolerance, and the functional role of the HLA molecule, specifically its role in immune recognition or as a membrane receptor for an infectious agent. The widespread distribution of B27 in the cells of the body versus the restricted anatomic distribution of the pathology of spondyloarthritis remains a major problem in explaining the association. Anterior uveitis, cardiac complications, and inflammation of the gastrointestinal and genitourinary tracts and other characteristic extraskeletal sites of involvement may reflect the basic disease process. Investigations need to focus on potential etiologic factors and their tropism for connective tissue at fibromuscular and fibroskeletal junctions, the cell mediated inflammatory response they precipitate, and their vascular routes to target sites.