4基因

本身可能并不致病，真正致病的基因与HLA-DR4连锁作用而导致妊高征。因此，对

HLA-DQ、HLA-DP区位点的研究也是很有必要的。

　　在母胎界面上，母体与胚胎细胞之间存在相互识别。母体识别胚胎的抗原，并

产生封闭抗体。一方面，封闭抗体与母体的细胞毒性淋巴细胞结合，封闭其细胞毒

作用，阻止它对胎儿的杀伤；另一方面，封闭抗体与胚胎细胞上的抗原结合，从而

阻断了母体的淋巴细胞到胚胎细胞的通路。现代免疫学认为，在器官移植中，供受

双方的HLA相容性越大，移植成功率越高。而在母胎界面上，母胎HLA相容性越大，

那么，母体就不能识别胚胎抗原，就不能产生封闭抗体，胚胎得不到封闭抗体的保

护而遭排斥，即产生病理性妊娠，如流产、不孕、妊高征、早产等。Kishore等［

20］在对数百例习惯性流产患者的研究中证实，夫妇共享HLA-A、HLA-DR的比例显

著增高，而其抗胚胎抗原的封闭抗体显著下降。

　　HLA-G是一种新发现的非经典HLA-Ⅰ类抗原，它在母胎界面上的独特分布引人

瞩目。它位于HLA远端300 bp以内，并且与HLA-Ⅰa类抗原有较高的同源性。HLA-G

于1987年被克隆［21］，1990年发现它在绒毛远端的细胞滋养层特异表达［22］。

它属于非经典的HLA-Ⅰb分子。与经典的HLA-Ⅰa的不同之处主要是：(1)HLA-G为单

态性，1995年WHO组织的HLA命名大会报道，HLA-G只有G*01011、G*01012、G*0102

、G*0103 4个等位基因［1］。(2)HLA-G分子结构上，分子胞内段很短，并且，由

于其mRNA的选择性剪切，产生不同的分子异构体为HLA-G1、G2、G3、G4、G5。(3)

HLA-G选择性地在胎盘表达，而HLA-Ⅰa及HLA-Ⅱ分子不在胎盘表达［23］。因此，

有人认为，HLA-G的表达可以保护胚胎免受母体淋巴细胞的攻击。体外混合淋巴细

胞培养表明，胚胎滋养层细胞不能刺激母体蜕膜NK细胞的增殖。有假说认为，HLA

-G能与母体蜕膜NK细胞的抑制性受体结合，并传入抑制性信号，从而抑制了母体蜕

膜NK细胞的活性，造成母体对胚胎抗原的免疫耐受；而胎盘HLA-G表达的下降会造

成病理性妊娠。Colbern等［24］的实验证实，在子痫前期患者中，胎儿终期胎盘

HLA-G表达降低。

　　目前，有关HLA-G与病理性妊娠相关性的研究还刚开始，值得探讨的问题还有

许多，那些与习惯性流产、原因不明的不孕症，妊高征相关联的HLA单倍体中，是

否带有特异的HLA-G等位基因，单态性的HLA-G表达的偏离以及母胎HLA-G的相容性

是否会影响着床(导致不孕症及妊高征)或者胚胎的生长(导致早产及低体重儿出生

)，可见，就HLA与病理性妊娠相关性的研究还应继续深入下去，这将对探讨病理性

妊娠的病因及预防提供理论依据。



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