Genetics of ankylosing spondylitis—insights into pathogenesis

To date, >40 genetic variants have been identified that influence the risk of developing ankylosing spondylitis (AS), including HLA alleles such as HLA-B27, among other, non-HLA allelesGenetic studies have also provided strong evidence of a role for the IL-23 pathway in AS pathogenesisOther pathways associated with AS include peptide handling prior to HLA presentation, innate and adaptive immune cell differentiation and activation, and bacterial sensing in the gutThe demonstration that patients with AS have a distinct gut microbiome is consistent with theories that AS is caused by IL-23-dependent interactions between the gut microbiome and the host immune systemData on AS genetics have provided preliminary support for the use of therapies targeting the IL-23 pathway and identified other potential targets, including aminopeptidases and the gut microbiomeStudies performed to date have uncovered less than one-third of the overall genetic risk in AS; new, larger studies should help define the immunopathogenesis of AS and related diseases