Zeliszewski D, Tiercy J M, Boitard C, Gu X F, Loche M, Krishnamoorthy R, Simonney N, Elion J, Bach J F, Mach B
Immunology Laboratory INSERM, Hôpital Robert Debre, Paris, France.
Hum Immunol. 1992 Feb;33(2):140-7. doi: 10.1016/0198-8859(92)90065-u.
To gain insight into the HLA subregions involved in protection against insulin-dependent diabetes mellitus (IDDM) we investigated the polymorphism of HLA-DR and -DQ genes in 23 DR2 IDDM patients. Results show the following. (1) Fourteen patients (61%) possess the DRB1, DRB5, and DQB1 alleles found in DRw16/DQw5 healthy people. These data contrast with the 5% of DRw16 normally found in DR2 populations and are in agreement with former observations supporting that the DRw16 haplotype is not protective. (2) Nine DR2 patients, i.e., 39% versus 95% in published DR2 controls, possess the DRB alleles found in DRw15 unaffected people. Among them, six patients have also DQA1 and DQB1 alleles identical to those found in DRw15/DQw6 healthy individuals. These data confirm that the DRw15/DQw6 haplotype is protective but indicate that none of the DR or DQ alleles, alone or in association, confers an absolute protection. (3) Our most striking results concern the very high frequency of recombinant haplotypes among the DRw15 patients: 3 of 9. In these three patients recombinations led to the elimination of both DQB1 and DQA1 alleles usually associated with DRw15. This strongly suggests that the occurrence of IDDM in these DRw15 patients is due to the absence of the usual DQ product and thus reinforces the assumption that DQ rather than DR region is involved in the protection conferred by the DRw15/DQw6 haplotype. Finally, analysis of the non-DRw15 haplotypes in heterozygous patients showed that IDDM can occur in the absence of any DQ alpha beta heterodimer of susceptibility.
为深入了解参与预防胰岛素依赖型糖尿病（IDDM）的HLA亚区域，我们研究了23例DR2 IDDM患者中HLA - DR和 - DQ基因的多态性。结果如下。（1）14例患者（61%）拥有在DRw16 / DQw5健康人群中发现的DRB1、DRB5和DQB1等位基因。这些数据与DR2人群中通常发现的5%的DRw16形成对比，并且与之前支持DRw16单倍型无保护作用的观察结果一致。（2）9例DR2患者，即39%（而在已发表的DR2对照中为95%）拥有在DRw15未患病个体中发现的DRB等位基因。其中，6例患者还具有与DRw15 / DQw6健康个体中发现的相同的DQA1和DQB1等位基因。这些数据证实DRw15 / DQw6单倍型具有保护作用，但表明没有任何一个DR或DQ等位基因单独或联合起来能提供绝对保护。（3）我们最显著的结果涉及DRw15患者中重组单倍型的频率非常高：9例中有3例。在这3例患者中，重组导致通常与DRw15相关的DQB1和DQA1等位基因均缺失。这强烈表明这些DRw15患者中IDDM的发生是由于缺乏通常的DQ产物，从而强化了这样一种假设，即DQ而非DR区域参与了DRw15 / DQw6单倍型所提供的保护作用。最后，对杂合患者中非DRw15单倍型的分析表明，在没有任何易感性DQαβ异二聚体的情况下也可能发生IDDM。
