Genetics and the pathogenesis of ankylosing spondylitis.
OBJECTIVE
The field of genetic research in ankylosing spondylitis (AS) is advancing rapidly. The purpose of this review is to outline recent findings, particularly, in regard to genetic studies of the major histocompatibility complex (MHC) and the non-MHC genes IL23R, ERAP1, and killer cell immunologlobulin-like receptor (KIR) complex, in AS.


RESULTS
Convincing evidence has been reported for the existence of further non-B27 MHC genes involved in AS. Strong, replicated association has been reported with IL23R and ERAP1 and AS. The IL23R finding strongly implicates the TH17 lymphocyte system in AS aetiopathogenesis. Suggestive evidence of a role for KIR gene polymorphism in AS exists, but definitive findings are awaited.


CONCLUSIONS
The findings suggest that further genome-wide studies in large case-control cohorts are likely to be very productive in this disease. The IL23R findings and subsequent immunological investigations suggest that targeted intervention in the TH17 system is likely to have major therapeutic benefit, as it does in the genetically related diseases, inflammatory bowel disease and psoriasis.
Brown
Matthew A
MA
Diamantina Institute of Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia. matt.brown@uq.edu.au
D000626:Aminopeptidases / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006649:Histocompatibility Antigens / Q000235:genetics*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D054340:Receptors, KIR / Q000235:genetics; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D006649:Histocompatibility Antigens; C515500:IL23R protein, human; D015778:Minor Histocompatibility Antigens; D018123:Receptors, Interleukin; D054340:Receptors, KIR; D000626:Aminopeptidases; C464841:ERAP1 protein, human