Olerup O, Smith C I, Hammarström L
Center for BioTechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
Nature. 1990 Sep 20;347(6290):289-90. doi: 10.1038/347289a0.
The human leukocyte antigens (HLA) are implicated in the genetic susceptibility to a large number of diseases. Some of the diseases associated with HLA class II are related to specific amino acids or epitopes of the domain of the HLA class II molecule that is distal to the membrane. In man, selective immunoglobulin A deficiency is the most common immunodeficiency, frequently resulting in recurrent sino-pulmonary infections and gastro-intestinal disorders. Associations have been described with HLA class I, and to a lesser extent with different class II alleles, which might indicate that they share some common feature. Here we study 95 IgA-D patients and find positive associations with three DR-DQ haplotypes and a strong negative association with a fourth haplotype. Comparison of the sequences of the polymorphic amino-terminal domain of the DQ beta chain showed that the three 'susceptibility' haplotypes all had a neutral alanine or valine at position 57. The 'protective' allele had the negatively charged aspartic acid at this position (Asp57). Codon 57 of the HLA-DQ beta chain has been implicated in the susceptibility to insulin-dependent diabetes mellitus. Our data suggest that the same amino acid position could possibly also influence susceptibility and resistance to selective immunoglobulin A deficiency.
人类白细胞抗原（HLA）与多种疾病的遗传易感性有关。一些与HLA II类相关的疾病与HLA II类分子膜远端结构域的特定氨基酸或表位有关。在人类中，选择性免疫球蛋白A缺乏症是最常见的免疫缺陷病，常导致反复的鼻窦肺部感染和胃肠道疾病。已有报道称其与HLA I类相关，与不同的II类等位基因的相关性较小，这可能表明它们具有一些共同特征。在这里，我们研究了95名IgA-D患者，发现与三种DR-DQ单倍型呈正相关，与第四种单倍型呈强负相关。对DQβ链多态性氨基末端结构域序列的比较表明，三种“易感”单倍型在第57位均具有中性的丙氨酸或缬氨酸。“保护性”等位基因在该位置具有带负电荷的天冬氨酸（Asp57）。HLA-DQβ链的第57密码子与胰岛素依赖型糖尿病的易感性有关。我们的数据表明，相同的氨基酸位置可能也会影响对选择性免疫球蛋白A缺乏症的易感性和抵抗力。
