Kumar U Shankar, Ghosh K, Gupte S S, Gupte S C, Mohanty D
HLA Department, Institute of Immunohaematology, 13th Floor, New MS Building, KEM Hospital, Parel, Mumbai 400 012, India.
J Biosci. 2002 Mar;27(2):135-41. doi: 10.1007/BF02703770.
Immunogenetic studies in various diseases provide potential genetic markers. We have studied the incidence of HLA A, B, C, DR and DQ loci antigen in Rh (D) antigen isoimmunized mothers compared to those nonimmunized isoimmunized Rh negative mothers. Seventy six mothers who were immunized to Rh (D) antigen due to pregnancy (responders) and fifty four mothers who did not develop Rh (D) isoimmunization despite positive pregnancies (nonresponders) were selected for the study. Standard methods of serological HLA typing, ABO and Rh (D) groups, and screening for Rh D antibodies were used. 392 unrelated individuals from the population were compared as controls. In addition 45 unrelated individuals from the same population were typed for HLA DRB and DQB gene using PCR-SSP kits. The genotype frequencies of HLA A2, A3, A28, B13, B17, B35, B52, B60, Cw2, Cw6, DR4, and DQ3 were significantly increased, while the frequencies of the HLA A11, A29, A31, B7, B37, B51, Cw1 and DR9 were decreased in the responder women when compared to the non-responder women. HLA A30 (19) split antigen was not identified in immunized women while HLA A23 (9) split antigen was not identified in non immunized women. HLA A3, B17, Cw2 and DR4 showed a significant relative risk among the immunized responder women. When compared with Rh immunized women (responders) reported from USA, England and Hungary the phenotype frequencies of HLA A11, A24, A28, B5, B17, B40, DR2 and DR5 were increased while HLA A23, B8, B18, and DR6 were decreased in the Indian Rh immunized women. Two locus haplotype frequency analysis observed among the responders women revealed that among the significant haplotypes expressed A2-B5, B7-Cw1, DR2-DQ1 were highly significant haplotypes in positive linkage, while A1-B5, and A1-B7 were in significant negative linkage disequilibrium. The haplotype frequencies were <or= one when these common hapoltypes were compared with control population. Thus in the present study it is evident that the inheritance of HLA A3, B17, Cw2 and DR4 increases the relative risk factor by 2.6 times among Indian Rh isoimmunized women. Further, it is evident that there are significant differences in the observed HLA antigen frequencies and two locus haplotypes in Rh isoimmunized women when compared to women from USA, UK and Hungary due to extreme HLA polymorphism in different populations of the world.
对各种疾病的免疫遗传学研究提供了潜在的遗传标记。我们研究了与未发生免疫反应的Rh阴性母亲相比，Rh（D）抗原免疫的母亲中HLA A、B、C、DR和DQ位点抗原的发生率。本研究选取了76名因妊娠而对Rh（D）抗原产生免疫反应的母亲（反应者）和54名尽管妊娠呈阳性但未发生Rh（D）同种免疫的母亲（无反应者）。采用血清学HLA分型、ABO和Rh（D）血型分组以及Rh D抗体筛查的标准方法。将来自该人群的392名无关个体作为对照。此外，使用PCR - SSP试剂盒对来自同一人群的45名无关个体进行HLA DRB和DQB基因分型。与无反应者相比，反应者女性中HLA A2、A3、A28、B13、B17、B35、B52、B60、Cw2、Cw6、DR4和DQ3的基因型频率显著增加，而HLA A11、A29、A31、B7、B37、B51、Cw1和DR9的频率降低。在免疫的女性中未鉴定出HLA A30（19）分裂抗原，而在未免疫的女性中未鉴定出HLA A23（9）分裂抗原。HLA A3、B17、Cw2和DR4在免疫的反应者女性中显示出显著的相对风险。与美国、英国和匈牙利报道的Rh免疫女性（反应者）相比，印度Rh免疫女性中HLA A11、A24、A28、B5、B17、B40、DR2和DR5的表型频率增加，而HLA A23、B8、B18和DR6的频率降低。在反应者女性中进行的两位点单倍型频率分析显示，在显著表达的单倍型中，A2 - B5、B7 - Cw1、DR2 - DQ1呈高度显著的正向连锁，而A1 - B5和A1 - B7呈显著的负向连锁不平衡。当将这些常见单倍型与对照人群进行比较时，单倍型频率≤1。因此，在本研究中很明显，HLA A3、B17、Cw2和DR4的遗传使印度Rh同种免疫女性的相对风险因素增加了2.6倍。此外，很明显，由于世界不同人群中HLA的极端多态性，与美国、英国和匈牙利的女性相比，Rh同种免疫女性中观察到的HLA抗原频率和两位点单倍型存在显著差异。
