Shindo Y, Ohno S, Yamamoto T, Nakamura S, Inoko H
Department of Ophthalmology, Yokohama City University School of Medicine, Japan.
Hum Immunol. 1994 Mar;39(3):169-76. doi: 10.1016/0198-8859(94)90257-7.
VKH disease is a bilateral panuveitis and has been known to be closely associated with the particular HLA class II antigens HLA-DR4 and -DQ4, defined by serologic typing. In this study, 63 Japanese VKH patients were analyzed for HLA class II alleles at the DNA level using the PCR-RFLP method. The DRB104 alleles encoding the serologic specificity DR4 were found in 100% of the VKH patients carrying DRB10405 or DRB10410. By statistical analysis, only DRB10405 was found to be significantly increased as compared to the healthy controls (RR = 46.7 and pc < 1 x 10(-5)). As to the DQB1 locus, all the patients carried DQB10401 or DQB10402 expressing the serologic DQ4 specificity, which is in a strong linkage disequilibrium with DRB10405 or DRB10410 in a Japanese population, respectively. Only DQB1*0401 showed a statistically significant increase as compared to the healthy controls (RR = 41.3 and pc < 1 x 10(-5)). Comparison of the amino acid sequences of these DRB1 and DQB1 alleles indicates that Ser at position 57 of DRB1 and/or Glu at position 70 and Asp at position 71 of DQB1 plays a crucial role in determining the susceptibility to VKH disease.
VKH病是一种双侧全葡萄膜炎，已知与通过血清学分型定义的特定HLA - II类抗原HLA - DR4和 - DQ4密切相关。在本研究中，使用PCR - RFLP方法在DNA水平分析了63例日本VKH患者的HLA - II类等位基因。在携带DRB10405或DRB10410的VKH患者中，100%发现了编码血清学特异性DR4的DRB104等位基因。通过统计分析，与健康对照相比，仅发现DRB10405显著增加（相对危险度 = 46.7，pc < 1×10⁻⁵）。关于DQB1位点，所有患者均携带表达血清学DQ4特异性的DQB10401或DQB10402，它们在日本人群中分别与DRB10405或DRB10410处于强连锁不平衡状态。与健康对照相比，仅DQB1*0401显示出统计学上的显著增加（相对危险度 = 41.3，pc < 1×10⁻⁵）。这些DRB1和DQB1等位基因氨基酸序列的比较表明，DRB1第57位的丝氨酸和/或DQB1第70位的谷氨酸和第71位的天冬氨酸在决定对VKH病的易感性方面起关键作用。
