Ankylosing spondylitis (AS) is the prototype of spondyloarthritis which shares complex clinical phenotypes and risk factors, both genetic and environmental with other chronic inflammatory disease, e.g. inflammatory bowel disease. Human leukocyte antigen-B27 has been known to be the major AS-susceptibility gene for more than 40 years and these molecules have distinct quaternary structures and biogenesis; at least three different hypotheses regarding the contributions to pathogenesis have been proposed. Advances in the discovery of novel susceptibility genes have pointed towards important biological pathways likely responsible for AS pathogenesis. As such, strong involvement of interleukin (IL)-23/IL-17 pathway has been hypothesized. The disease is characterized by inflammation and ankylosis, mainly at the cartilage−bone interface and enthesis. Besides the genetic background, environmental triggers such as microorganisms and mechanical stress are emerging as initiating and perpetuating factors for AS. Current concepts regard new bone formation at the enthesis as a pathological response to biomechanical stress and microbial consequences such as dysbiosis in gut inflammation. (J Rheum Dis 2015;22:61-68)

Keywords: Ankylosing spondylitis, Pathogenesis, Mechanical stress, Enthesopthy, Interleukin-23