杀伤细胞免疫球蛋白样受体及其配体HLA-C基因多态性与不明原因早期复发性流产的相关性

Association of killer-immunoglobulin-like receptors/human leukocyte antigen(HLA)-C and early recurrent spontaneous abortion

目的:探讨杀伤细胞免疫球蛋白样受体及其配体HLA-C基因多态性与不明原因早期复发性流产易感性的关系。方法:留取不明原因早期复发性流产患者(38例,URSA组)及正常早孕妇女(35例,对照组)的蜕膜、绒毛组织,抽提基因组DNA,序列特异性引物聚合酶链反应检测蜕膜组织14种KIR基因的表达;DNA测序法分析绒毛滋养细胞HLA-C1、HLA-C2基因多态性。结果:14种KIR基因均以不同频率表达;KIR2DS1基因的频率在URSA组与对照组中分别为60.27%vs41.18%,两组相比,差异有显著性(P=0.03)。两组基因HLA-C1、HLA-C2在绒毛组织中呈不平衡表达,以HLA-C1基因占明显优势。URSA组与对照组HLA-C1基因频率分别为66.67%、81.03%,两组相比差异无显著性,P=0.657;URSA组HLA-C2的基因频率为33.33%,对照组HLA-C2的基因频率为19.07%,两组相比差异有显著性,P=0.007。结论:蜕膜NK细胞活化性KIR基因频率升高,与绒毛滋养细胞的HLA-C2基因结合,传递活化性信号活化NK细胞,可能是引起URSA发病的免疫遗传学因素之一。

Objective：To study the relationship between the genotypes of killer-immunoglobulin-like receptors and of human leukocyte antigen（HLA）-C molecules on trophoblast cells in decidua and the susceptiblity to early unexplained recurrent spontaneous abortion.Methods：Decidual and trophoblast samples were obtained from the patients（n=38） who suffered from recurrent spontaneous abortion and from the normal pregnant women（n=35）.Sequence-specific primer polymerase chain reaction（PCR-SSP） was used to determine the individual KIR genotypes in women undergoing URSA and controls.Genotypes were detected for HLA-C1 and HLA-C2 by sequence-based typing.Results：A higher prevalence of activating KIR genes was seen in URSA patients than in controls.Among women undergoing URSA,the gene frequence of KIR2DS1 was more prevalent（60.27% vs 41.18%,P=0.03） compared with controls.The haplotype of HLA-C1 showed the highest frequencies in both groups.There was no significant differences in the frequencies of HLA-C1 molecules on trophoblast cells between the two groups（66.67% vs 81.03%,P=0.657）.But there was higher frequencies of HLA-C2 molecules in the patients than in the control（33.33% vs 19.07%,P=0.007）.Conclusion：The increased frequencies of KIR2DS1 and HLA-C2 genes on trophoblast cells might confer to the pathogenesis of early recurrent spontaneous abortion.