Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency.
Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency.
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主要组织相容性复合物 III 类基因以及对免疫球蛋白 A 缺陷和常见变异型免疫缺陷的易感性。
DOI：
10.1172/jci115797
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Cooper,MD
中科院分区：
文献类型：
--
作者：
Volanakis,JE;Zhu,ZB;Schaffer,FM;Macon,KJ;Palermos,J;Barger,BO;Go,R;Campbell,RD;SchroederJr,HW;Cooper,MD
我们提出，IgA缺乏症(IgA-D)和常见可变免疫缺陷(CVID)患者的显著亚群可能代表临床谱的两极，反映单一潜在的遗传缺陷。这一建议得到了我们的发现的支持，即患有这些免疫缺陷的人有共同的C4a基因缺失和C2罕见基因等位基因的高发生率。在此，我们分析了21个家系的12名IgA-D和19名CVID个体及其79名直系亲属的MHC单倍型。通过分析HLADQB1和HLAA基因之间11个基因或其产物的多态标记来确定MHC单倍型。在接受调查的五个家庭中，有五个家庭包含一个以上的免疫缺陷个体，所有这些家庭都包括IgA-D和CVID成员。对数据的分析表明，大多数免疫缺陷个体都有少量的MHC单倍型。在31名免疫缺陷个体中，有24名(77%)至少存在两种单倍型中的一种。这些单倍型在IgA-D和CVID个体之间的分布没有差异。对这些单倍型的详细分析表明，一个或两个免疫缺陷的易感基因位于MHC的III类区域，可能位于C4b和C2基因之间。
We have proposed that significant subsets of individuals with IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) may represent polar ends of a clinical spectrum reflecting a single underlying genetic defect. This proposal was supported by our finding that individuals with these immunodeficiencies have in common a high incidence of C4A gene deletions and C2 rare gene alleles. Here we present our analysis of the MHC haplotypes of 12 IgA-D and 19 CVID individuals from 21 families and of 79 of their immediate relatives. MHC haplotypes were defined by analyzing polymorphic markers for 11 genes or their products between the HLA-DQB1 and the HLA-A genes. Five of the families investigated contained more than one immunodeficient individual and all of these included both IgA-D and CVID members. Analysis of the data indicated that a small number of MHC haplotypes were shared by the majority of immunodeficient individuals. At least one of two of these haplotypes was present in 24 of the 31 (77%) immunodeficient individuals. No differences in the distribution of these haplotypes were observed between IgA-D and CVID individuals. Detailed analysis of these haplotypes suggests that a susceptibility gene or genes for both immunodeficiencies are located within the class III region of the MHC, possibly between the C4B and C2 genes.Images