Sir Norman Gregg Lecture

Anterior uveitis and HLA B27- progress at last!

Despite being the commonest cause of uveitis, the pathogenesis of HLA-B27-associated anterior uveitis (AU) has remained an enigma since its description 40 years ago. Recent studies from our laboratory and others has given greater insight into the role of genetic factors, microbial triggers, and the role of immune and molecular mechanisms in the pathogenesis of this disease.

The clinical features and associated systemic disease in HLA B27 individuals are distinctive and consistent across different populations. HLA B27 AU is polygenic with a number of genes predisposing to ocular inflammation, particularly ERAP-1, which has a role in antigen processing and presentation via HLA B27 on the cell surface. The microbiome and an increasing number of microorganisms have been implicated in AU and serological evidence of previous Chlamydial trachomatis (CT) infection is present up to 50% of patients with AU. We have shown that peptides derived from CT selectively bind to the HLA B27 molecule and induce arthritis and AU when injected into experimental animals. Cytokines, adhesion molecules, Toll like receptors and proteases play a critical role in the pathogenesis of AU. Molecular studies have revealed new therapeutic approaches to the treatment HLA B27 AU, such as anti-TNF-alpha therapy, which prevents relapses and has the potential to change the natural history of this disease.