Islam S M, Numaga J, Fujino Y, Hirata R, Matsuki K, Maeda H, Masuda K
Department of Ophthalmology, University of Tokyo School of Medicine, Japan.
Invest Ophthalmol Vis Sci. 1994 Oct;35(11):3890-6.
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.
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.
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-DQA10301 genotype, which was present in only 67% of the normal controls (relative risk, 56.5; Pc < 1.0 x 10(-5)). With allelic combinations, -DQA10301/-DR4 showed the greatest relative risk ratio. Conversely, DQB1*0604 genotype was not detected among the patients.
It can be postulated that VKH is a disease of combined allelic predisposition in which DQA10301 acts as the primary and HLA-DR4 acts as an additive factor in the development of the disease. Based on the negative association of DQB10604, we propose that DQB1*0604 provides considerable protection, possibly by altering other factors in the pathogenesis of VKH in the Japanese.
伏格特-小柳-原田病（VKH）是一种自身免疫性疾病，可引起双侧弥漫性肉芽肿性葡萄膜炎，常伴有多种相关的眼外表现。人类白细胞抗原（HLA）抗原与该病的强关联已有文献记载。本研究对日本VKH患者的所有HLA II类基因型细节进行了调查，以阐明该疾病的免疫遗传背景。
采用改良的两阶段补体依赖微量细胞毒性法对57例日本VKH患者进行人类白细胞抗原组织分型。通过聚合酶链反应（PCR）-单链构象多态性和PCR-限制性片段长度多态性方法进行DNA分析。
VKH患者中HLA-DR4和HLA-DQ4的频率分别为93%和83%，而对照组分别为43%和32%（相对风险分别为17.4和9.9；Pc<1.0×10⁻¹⁰）。在基因水平上，所有患者均具有HLA-DQA10301基因型，而该基因型在正常对照组中仅占67%（相对风险为56.5；Pc<1.0×10⁻⁵）。在等位基因组合中，-DQA10301/-DR4显示出最大的相对风险比。相反，患者中未检测到DQB1*0604基因型。
可以推测VKH是一种联合等位基因易感性疾病，其中DQA10301起主要作用，HLA-DR4在疾病发展中起附加作用。基于DQB10604的负相关关系，我们提出DQB1*0604可能通过改变日本VKH发病机制中的其他因素而提供显著的保护作用。
