Current ResearchAcute Anterior Uveitis and HLA-B27
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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Scrotal pain of a patient with ankylosing spondylitis successfully treated with TNF-alpha inhibitor: a case report
2024, Journal of Orthopaedic ScienceCitation Excerpt :Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease that affects the axial skeleton, causing characteristic inflammatory back pain, which can lead to structural and functional impairments and a decrease in quality of life [1,2]. AS affects males about twice as often as females, and the major histocompatibility complex (MHC) class I molecule human leukocyte antigen (HLA)-B27 is strongly known as contributing factor of AS [1,3]. With the advent of biologic agents, including tumor necrosis factor (TNF)-α inhibitors, significant improvement in clinical symptoms can be expected [1,4].
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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.