The genetics of spondyloarthropathies

Spondyloarthropathies are a heterogeneous group of rheumatic disorders that commonly present with axial skeleton or sacroiliac joints involvement. Ocular involvement like uveitis, iritis and conjunctivitis can be present in up to a third of the patients. Genetic factors play a part in the pathogenesis of spondyloarthropathies. Association with the HLA-B27 gene, especially that between ankylosing spondylitis and HLA-B27 antigenic positivity, is one of the strongest association seen between a disease and a Class I antigen. This paper aims to review the frequencies of HLA-B27 gene and its subtypes in different population groups, possible mechanisms leading to the development of joint inflammation and the risk it confers for development of spondyloarthropathies.

The MEDLINE database was searched using keywords: HLA-B27, spondyloarthropathy, molecular mimicry, arthritogenic peptides, reactive arthritis and ankylosing arthritis. Related articles for selected papers were also consulted. Books on HLA-B27 and spondyloarthropathy were obtained through the NUS Medical Library's LINC system.

The genetic subtypes and susceptibility to development of disease vary in different population groups. Other HLA genes and non-HLA genes also play a part in the development of spondyloarthropathies, especially in those who are HLA-B27 negative. HLA-B27-positive relatives of spondyloarthritics have a higher risk of developing a similar condition. The presence of the HLA-B27 gene may serve as an aid to diagnosis or prognosis for clinicians. In juvenile arthritic patients, it is a poor prognostic factor, predicting for disease severity. It is also associated with poor outcomes for patients with anterior uveitis. However screening of asymptomatic individuals for the HLA-B27 gene is not recommended.

The polygenic nature of the disease needs further elucidation and study.