| Objectives: Vitiligo is a common skin disorder characterized by depigmentation. Factors contributing to the development of vitiligo remain largely unknown. However, a number of hypotheses exist to explain the aetiology: neurochemical-mediated effects on melanocytes, intrinsic melanocyte defect and autoimmunity. These theories are not mutually exclusive, and it is easy to imagine that autoimmunity might arise as a secondary phenomenon in response to melanocyte damage by other mechanisms. The immunological aspects of vitiligo are well documented. It is suggested that genetic factors may play a role in the development of vitiligo. Over 20% of patients have family history of vitiligo. Several studies have reported associations of vitiligo with certain human leucocyte antigen (HLA) specilicities, but there is no consistent association with any of the MHC class â… or class â…¡ alleles. If vitiligo is in part an autoimmune disorder, genetic factors that predispose an individual to autoimmunity may influence the development of the disease. Mounting an appropriate immune response depends on the careful regulation of lymphocyte activation. T-cell responses are regulated by activating and inhibitingsignals. Studies of some autoimmune disorders have shown that the production of autoantibodies by B cells is dependent upon stimulation from CD4+ T cells. Cytotoxic T lymphocyte associated-4 (CTLA-4) has been reported to be an important negative regulator of autoimmune diseases. CTLA-4 located on chromosome 2q33, a member of the same family of cell surface molecules as CD28, is involved in the regulation of T cells. Both of these molecules bind to B7 on APC cells and the CTLA4-B7 complex can compete with the CD28/B7 complex and deliver negative signals to the T cell affecting T cell proliferation, cytokine production, and immune responses. The functional importance of CTLA-4 is emphasised by the demonstration that CTLA-4-deficient mice develop lethal self-reactive lympho-proliferative disease, demonstrating that CTLA-4 acts as a negative regulator of T-cell activation and is vital for the control of lymphocyte homeostasis. In theory, reduced expression or aberrant function of CTLA-4 may lead to autoimmune T cell clonal proliferation and contribute to the pathogenesis of autoimmune diseases. Three CTLA-4 gene polymorphisms in humans (in the promoter at position 318 from the ATG start codon, at position 49 in exon 1, and in an (AT)n repeat within the 3'-untranslated region of exon 3 ) have been published. Recent studies showed that CTLA-4 gene polymorphism was associated with several kinds of human autoimmune diseases, suggesting that CTLA-4 gene isprobably a general susceptibility gene to autoimmune disease. A threonine to alanine (A-G) polymorphism at position 49 in exon 1, has been reported to be associated with both Graves' disease and type I diabetes. As vitiligo is frequently associated with autoimmune disorders and may have an autoimmune origin, we investigate the frequency of the A-G polymorphism of the CTLA-4 gene in a hospital based case-control study to determine whether the CTLA-4 gene plays a part in genetic susceptibility to Vitiligo. Materials and Methods: 59 patients with vitiligo were recruited from the dermatology department of the Fourth Affiliated Hospital of Hebei Medical University from December, 2001 to November, 2002. Vitiligo was diagnosed on the basis of clinical and laboratory evidence, all patients met ZhuWenyuan's diagnostic criteria. The vitiligo patients include 24 males and 35 females; age range from 9 to 66 (average 29); course from 0.5 months to 37 years (average 44 months); active phrase 43 and stable phrase 16; with one or more autoimmune diseases 14, without any other autoimmune disorder 45. 124 healthy volunteers who had no clinical evidence of vitiligo or any other autoimmune disorder , as control subjects, were randomly selected from Chinese blood donors. The controls include 67 males and 57 females; age range from 18 to 60 (average 30). All subjects gave i... |
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