Shindo Y, Inoko H, Yamamoto T, Ohno S
Department of Ophthalmology, Yokohama City University School of Medicine, Japan.
Br J Ophthalmol. 1994 Mar;78(3):223-6. doi: 10.1136/bjo.78.3.223.
Vogt-Koyanagi-Harada's (VKH) disease is reported to be closely associated with the HLA class II antigen, HLA-DR4. Serologically defined DR4 is further divided into 11 alleles by molecular HLA genotyping. However, no study of HLA-DNA typing of VKH patients has been reported. To clarify molecular genetic mechanism underlying the susceptibility/resistance to VKH disease, HLA-DNA typing of DR antigens (DRB1 genotyping) by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed. It was found that DRB10405 showed a significant association with VKH disease compared with the healthy controls (corrected p value < 1 x 10(-5)) and that all the patients had DRB10405 and/or DRB10410. The specific amino acid residue shared only by these two alleles is Ser at position 57 which is located in the antigen binding groove and may influence the immunological function as an antigen-presenting molecule, suggesting that Ser at position 57 plays an important role in the susceptibility to VKH disease, although the possibility that the involvement of the HLA-DQ molecule, DQ4, in strong linkage disequilibrium with DRB10405 and DRB1*0410, cannot be excluded.
据报道，Vogt-小柳原田病（VKH）与人类白细胞抗原（HLA）II类抗原HLA-DR4密切相关。通过分子HLA基因分型，血清学定义的DR4可进一步分为11个等位基因。然而，尚未有关于VKH患者HLA-DNA分型的研究报道。为了阐明VKH病易感性/抗性的分子遗传机制，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对DR抗原进行HLA-DNA分型（DRB1基因分型）。结果发现，与健康对照相比，DRB10405与VKH病存在显著关联（校正p值<1×10⁻⁵），且所有患者均具有DRB10405和/或DRB10410。这两个等位基因仅共有的特定氨基酸残基是位于抗原结合槽中的第57位丝氨酸，它可能作为抗原呈递分子影响免疫功能，这表明第57位丝氨酸在VKH病易感性中起重要作用，尽管不能排除与DRB10405和DRB1*0410处于强连锁不平衡状态的HLA-DQ分子DQ4的参与可能性。
