Progress in the genetics of uveitis

Abstract

Uveitis is the most common form of intraocular inflammatory disease and is a significant cause of visual impairment worldwide. Aetiologically, uveitis can also be classified into infectious uveitis and non-infectious uveitis. The common non-infectious forms of uveitis include acute anterior uveitis (AAU), Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, birdshot chorioretinopathy (BSCR), sarcoid uveitis. In addition, a few monogenic autoinflammatory disorders can also cause uveitis, such as Blau Syndrome and haploinsufficiency of A20 (HA20). Although the exact pathogenesis of non-infectious uveitis is still unclear, it is well-recognised that it involves both genetic and environmental risk factors. A hallmark of uveitis is its strong associations with human leucocyte antigens (HLA). For examples, AAU, BD and BSCR are strongly associated with HLA-B27, HLA-B51, and HLA-A29, respectively. In uveitis studies, multiple GWAS have successfully been conducted and led to identification of novel susceptibility loci, for example, IL23R has been identified in BD, VKH and AAU. In this review, we summarize the latest progress on the genetic associations of both HLA and non-HLA genes with major forms of uveitis, including AAU, BD, VKH, BSCR, sarcoid uveitis, Blau Syndrome and HA20, and potential future research directions.

Fig. 1. Positive (PPV) and negative predictive values (NPV) for patients with AS with AAU for centiles of genetic risk scores [10].

The prevalence of patients with both AS and AAU is assumed to be 0.3% among the general population, and 20% in AS patients attending rheumatology outpatient clinics.

Fig. 2. Positive (PPV) and negative predictive values (NPV) of PRS and HLA-B27 for AS [24].

Positive (PPV) and negative predictive values (NPV) of Polygenic Risk Scores (PRS) and HLA-B27 for ankylosing spondylitis (AS). The prevalence of AS is assumed to be 30%, the likely prevalence of AS amongst patients <45 years of age attending outpatient services with chronic back pain lasting >3 months.