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S M Islam, J Numaga, Y Fujino, R Hirata, K Matsuki, H Maeda, K Masuda; HLA class II genes in Vogt-Koyanagi-Harada disease.. Invest. Ophthalmol. Vis. Sci. 1994;35(11):3890-3896.
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PURPOSE: Vogt-Koyanagi-Harada disease (VKH) is an autoimmune disorder causing a bilateral diffuse granulomatous uveitis, often with several associated extraocular manifestations. Strong association of human leukocyte antigens (HLA) antigens with the disease has been documented. The details of all HLA class II genotypes were investigated in Japanese patients with VKH to demonstrate the immunogenetic background of the disease. METHODS: Human leukocyte antigen tissue typing was performed in 57 Japanese patients with VKH by the modified two-stage complement-dependent microcytotoxicity method. DNA analyses were done by polymerase chain reaction (PCR)-single-strand conformation polymorphism and PCR-restriction fragment-length polymorphism methods. RESULTS: The frequencies of HLA-DR4 and HLA-DQ4 were 93% and 83% among the patients with VKH, compared with 43% and 32% among the controls, respectively (relative risks, 17.4 and 9.9; Pc < 1.0 x 10(-10)). At the genomic level, all patients had the HLA-DQA1*0301 genotype, which was present in only 67% of the normal controls (relative risk, 56.5; Pc < 1.0 x 10(-5)). With allelic combinations, -DQA1*0301/-DR4 showed the greatest relative risk ratio. Conversely, DQB1*0604 genotype was not detected among the patients. CONCLUSION: It can be postulated that VKH is a disease of combined allelic predisposition in which DQA1*0301 acts as the primary and HLA-DR4 acts as an additive factor in the development of the disease. Based on the negative association of DQB1*0604, we propose that DQB1*0604 provides considerable protection, possibly by altering other factors in the pathogenesis of VKH in the Japanese.
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