SHARED HLA CLASS-II-ASSOCIATED GENETIC SUSCEPTIBILITY AND RESISTANCE, RELATED TO THE HLA-DQB1 GENE, IN IGA DEFICIENCY AND COMMON VARIABLE IMMUNODEFICIENCY
SHARED HLA CLASS-II-ASSOCIATED GENETIC SUSCEPTIBILITY AND RESISTANCE, RELATED TO THE HLA-DQB1 GENE, IN IGA DEFICIENCY AND COMMON VARIABLE IMMUNODEFICIENCY
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DOI：
10.1073/pnas.89.22.10653
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发表时间：
1992-11-15
影响因子：
11.1
通讯作者：
HAMMARSTROM, L
中科院分区：
文献类型：
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作者：
OLERUP, O;SMITH, CIE;HAMMARSTROM, L
大多数选择性伊加缺乏症（IgA-D）和常见变异型免疫缺陷症（CVID）的病例是偶发性的。然而，家族聚集性并不罕见，这两种疾病可以发生在同一个家庭中。我们先前已经描述了与三种DR-DQ单倍型的正相关以及与IgA-D中的DRw 15、DQw 6、Dw 2的强负相关。发现HLA-DQ β链57位的不同氨基酸与对IgA-D的易感性和抗性相关。现在，我们在一个大的CVID患者组（n = 86）中发现了相同的，尽管有些弱，阳性和阴性的DR-DQ关联，以及与DQB 1基因密码子57的相同关联。此外，我们已经证实了我们早期的观察，在一个独立的一组IgA-D的个人（n = 69），并在同胞对分析中，我们发现了连锁的遗传易感性IgA-D的HLA II类区域。在IgA-D个体不携带三个过度表达的DR-DQ单倍型，同样的积极协会与非天冬氨酸残基的HLA-DQ β链的位置57被视为。先前报道的与HLA III类基因C4 A（补体第四成分）和CYP 21 P（类固醇21-羟化酶假基因）缺失的相关性，在我们的免疫缺陷个体组中，在统计学上仅次于与DQB 1等位基因0201的相关性。这两种体液免疫缺陷中共有的HLA-II类相关性支持IgA-D和CVID相关的假设。疾病易感性和抗性与DR-DQ区域内的基因最密切相关，DQB 1基因座的等位基因是候选基因。
Most cases of selective IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) occur sporadically. However, familial clustering is not uncommon, and the two disorders can occur within the same family. We have previously described positive associations with three DR-DQ haplotypes as well as a strong negative association with DRw15,DQw6,Dw2 in IgA-D. Different amino acids at position 57 of the HLA-DQbeta chain were found to be related to susceptibility and resistance to IgA-D. Now we have found identical, although somewhat weaker, positive and negative DR-DQ associations in a large group of CVID patients (n = 86), as well as the same associations with codon 57 of the DQB1 gene. In addition, we have confirmed our earlier observations in an independent group of IgA-D individuals (n = 69), and in sib-pair analysis we have found linkage of the genetic susceptibility to IgA-D to the HLA class II region. In IgA-D individuals not carrying the three overrepresented DR-DQ haplotypes, the same positive association with a non-aspartic acid residue at position 57 of the HLA-DQbeta chain was seen. The previously reported associations with deletions of the HLA class III genes C4A (fourth component of complement) and CYP21P (steroid 21-hydroxylase pseudogene) were, in our groups of immunodeficient individuals, statistically secondary to the association with the DQB1 allele 0201. The shared HLA class II associations in the two humoral immunodeficiencies support the hypothesis that IgA-D and CVID are related disorders. Disease susceptibility and resistance are most closely associated with a gene(s) within the DR-DQ region, alleles of the DQB1 locus being candidate genes.