HLA-G polymorphisms in couples with recurrent spontaneous abortions
HLA-G polymorphisms in couples with recurrent spontaneous abortions
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DOI：
10.1034/j.1399-0039.2002.600202.x
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发表时间：
2002-08-01
期刊：
影响因子：
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通讯作者：
Christiansen, OB
中科院分区：
文献类型：
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作者：
Hviid, TV;Hylenius, S;Christiansen, OB
部分复发性自然流产（RSA）的病因可能涉及免疫机制。异常概况的Th1和Th2细胞因子已被观察到不存在于无并发症的妊娠。经典HLA I类和II类抗原与RSA的关系的研究尚无定论。此外，除了HLA-C外，这些抗原在胎盘中不表达。然而，HLA-G在侵袭性细胞滋养细胞上表达，并以膜和可溶性形式存在。HLA-G可能与母胎耐受有关。因此，61对RSA夫妇（三次或三次以上自然流产）和47对生育对照夫妇通过直接DNA测序进行HLA-G基因分型并分析特异性多态性。在对照组和RSA夫妇之间HLA-G等位基因的分布没有统计学上的显著差异，然而，15%的RSA女性携带HLA-G*0106等位基因，而对照组女性只有2%。另外对8外显子14bp缺失多态性进行了研究。根据Hardy-Weinberg平衡，在生育控制组中，14bp多态性的杂合子数量比预期的要多。此外，不含14bp序列的HLA-G等位基因在RSA男性中突出，而在RSA女性中则经常观察到含有14bp序列的等位基因，尤其是纯合子。这些结果讨论了两个假设有关HLA-G和RSA。胎儿/胎盘与母亲之间HLA-G组织不相容的假设没有得到数据的支持。另一种假说涉及某些HLA-G等位基因与HLA-G异构体的表达谱改变或某些HLA-G异构体的表达减少有关。
The etiology of a fraction of recurrent spontaneous abortions (RSA) may involve immunological mechanisms. Aberrant profiles of Th1 and Th2 cytokines have been observed which are not present in uncomplicated pregnancies. Studies of classical HLA class I and II antigens in relation to RSA have not been conclusive. Furthermore, these antigens are not expressed in the placenta with the exception of HLA-C. However, HLA-G is expressed on especially invasive cytotrophoblasts and exists in both membrane and soluble forms. HLA-G may be involved in materno-fetal tolerance. Therefore, 61 RSA couples (with three or more spontaneous abortions) and 47 fertile control couples were HLA-G genotyped by direct DNA sequencing and analyzed for specific polymorphisms. No statistically significant differences were observed in the distribution of HLA-G alleles between controls and RSA couples, however, 15% of the RSA women carried the HLA-G*0106 allele compared to 2% of the control women. The 14 bp deletion polymorphism in exon 8 was investigated separately. There were a greater number of heterozygotes for the 14 bp polymorphism in the group of fertile control women than expected, according to Hardy-Weinberg equilibrium. Furthermore, the HLA-G alleles without the 14 bp sequence were prominent in the RSA males in contrast to the RSA women in whom alleles including the 14 bp sequence were frequently observed, especially as homozygotes. These results are discussed in relation to two hypotheses concerning HLA-G and RSA. A hypothesis of HLA-G histo-incompatibility between fetus/placenta and the mother was not supported by the data. Another hypothesis concerned certain HLA-G alleles associated with an altered expression profile of HLA-G isoforms or reduced expression of certain HLA-G isoforms.