Complete Association of the HLA-DRB1*04 and -DQB1*04 Alleles with Vogt-Koyanagi-Harada's Disease

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 DRB1*04 alleles encoding the serologic specificity DR4 were found in 100% of the VKH patients carrying DRB1*0405 or DRB1*0410. By statistical analysis, only DRB1*0405 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 DQB1*0401 or DQB1*0402 expressing the serologic DQ4 specificity, which is in a strong linkage disequilibrium with DRB1*0405 or DRB1*0410 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.