Elsevier

Survey of Ophthalmology

Volume 50, Issue 4, July–August 2005, Pages 364-388
Survey of Ophthalmology

Current Research
Acute Anterior Uveitis and HLA-B27

https://doi.org/10.1016/j.survophthal.2005.04.003Get rights and content

Abstract

Acute anterior uveitis is the most common form of uveitis. HLA-B27-associated acute anterior uveitis is a distinct clinical entity that has wide-ranging medical significance due to its ocular, systemic, immunologic, and genetic features. The association between HLA-B27 and the spectrum of HLA-B27-associated inflammatory diseases remains one of the strongest HLA-disease associations known to date. This review examines acute anterior uveitis with particular focus on HLA-B27-associated acute anterior uveitis, including the epidemiology, immunopathology, association with HLA-B27 and its subtypes, clinical features, complications, prognosis, and potential new therapies such as anti-TNFα therapy and oral HLA-B27-peptide tolerance. There have been substantial recent advances in both clinical and basic scientific research in this field, including studies of the various animal models of acute anterior uveitis and the HLA-B27 transgenic animals, and these are summarized in this review. To the ophthalmologist, HLA-B27-associated acute anterior uveitis is an important clinical entity that is common, afflicts relatively young patients in their most productive years, and is associated with significant ocular morbidity due to its typically recurrent attacks of inflammation and its potentially vision-threatening ocular complications. Furthermore, to the ophthalmologist and the internist, HLA-B27-associated acute anterior uveitis is also of systemic importance due to its significant association with extraocular inflammatory diseases.

Introduction

Uveitis is the most common form of inflammatory eye disease and an important cause of visual impairment and blindness.176 Given that uveitis predominantly affects the young adult population in their most productive years and, not uncommonly, also affects children, the personal and population burden of its sight-threatening effects are significant. The association between the human major histocompatibility complex (MHC), HLA (human leukocyte antigen)-B27, and its spectrum of HLA-B27-associated inflammatory diseases (Table 1) and acute anterior uveitis (AAU) was originally described in 1973 and remains one of the strongest HLA-disease associations.26, 27, 28, 187 Despite intensive clinical and basic scientific research, the precise molecular and pathogenic mechanisms linking HLA-B27 and its associated inflammatory diseases remains unclear. However, in recent years, HLA-B27-related research has resulted in significant advances in our understanding of the immunopathogenesis of these diseases by providing critical new information, which often leads us to newer questions but at the same time brings us a step closer to unraveling the complexities of the underlying disease mechanism.

HLA-B27 AAU has significant systemic disease associations and is thus of specific interest to the internist as well as the ophthalmologist. Among the various uveitides and their associated systemic diseases, HLA-B27 AAU and its related systemic inflammatory conditions is, by far, the most common. Thus, understanding the relationship between AAU and HLA-B27 antigen is of wide ranging medical significance.

Section snippets

Anterior Uveitis

Uveitis is a relatively common inflammatory eye disease with reported annual incidences of between 17 and 52.4 per 100,000 person-years46, 71, 149, 204, 208 and prevalence of between 38 and 370 per 100,000 population.45, 46, 71, 149, 208 Uveitis most commonly afflicts those aged between 20 and 50; it is uncommon in the very young (under 10 years of age) and the very old (over 70 years of age).128, 150, 168, 174, 192, 214 Of people aged under 65 who are registered legally blind, 10% are visually

Structure and Function of HLA Molecules

The human leukocyte antigens are encoded by genes located within the major histocompatibility complex on the short arm of chromosome 6. The MHC contains in excess of 220 genes in three major gene clusters. The class I genes encode for the classical transplantation antigens HLA-A, -B and -C, and the non-classical class I molecules, HLA-E, -F and -G. The class II genes encode for the HLA-D molecules including HLA-DR, -DQ, and -DP, and the class III genes encode for the complement proteins C2, C4,

Animal Models of Acute Anterior Uveitis

Research into the pathogenesis of uveitis has been facilitated by the development of several animal models, allowing in vivo studies directed at specific steps and mediators of inflammation. The ethical and practical limitations involved in obtaining human ocular tissues during active uveitis or at multiple time points over the course of disease prevent such human studies. Consequently, most of our knowledge is derived from studies of animal models. Despite the similarities, there are also

Pathogenesis of HLA-B27 Acute Anterior Uveitis

It is clear from the evidence of epidemiological and experimental studies, including those of HLA-B27 transgenic animals, that both genetic and environmental factors are critically important in the pathogenesis of HLA-B27-associated diseases. The SpA are multifactorial diseases that occur in genetically predisposed persons and are triggered by environmental factors, although the identity of these factors and their precise mechanisms have not yet been elucidated. Much of the research aimed at

Potential New Therapies

Topical corticosteroids and cycloplegic agents form the mainstay of therapy for the great majority of HLA-B27 AAU with good ocular outcome in most cases. However, complications may occur in HLA-B27 AAU, such as CME, and such severe or sight-threatening uveitis may require more aggressive therapy in the forms of periocular corticosteroids, systemic corticosteroids, and/or systemic immunosuppressive agents. Current therapies for uveitis are non-specific in their mode of action and have a number

Conclusions

HLA-B27 AAU is a common form of inflammatory eye disease that forms a distinct clinical entity of wide-ranging medical significance due to its potentially sight-threatening ocular complications, associated ocular morbidity due to recurrent attacks of inflammation, and its significant association with systemic diseases. Recent advances in clinical and experimental research have shed much light on the complex genetic, environmental, and immunologic components to the etiopathogenesis of this

Method of Literature Search

Literature selection for this article was based initially on a medline database (1966–present) search using the following key words: HLA-B27, uveitis, anterior uveitis, seronegative spondyloarthropathy, immunology, and pathology. References were also obtained from major textbooks, such as Pepose JS, Holland GN, Wilhelmus KR, eds: Ocular Infection and Immunity (Mosby-Yearbook, 1996) and manual searches based upon reference lists of the retrieved articles from the initial search. Given the

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    Dr John H. Chang is a recipient of the NH&MRC Medical Postgraduate Research Scholarship (grant 222928). The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.

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