Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success.
Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success.
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母体KIR和胎儿HLA-C基因的组合会影响先兆子痫和生殖成功的风险。
DOI：
10.1084/jem.20041214
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发表时间：
2004-10-18
影响因子：
15.3
通讯作者：
Moffett, A
中科院分区：
文献类型：
--
作者：
Hiby, SE;Walker, JJ;O'Shaughnessy, KM;Redman, CWG;Carrington, M;Trowsdale, J;Moffett, A
先兆子痫是一种严重的妊娠并发症，其中胎儿由于滋养层侵入失败而接受的血液供应不足。有证据表明，这种情况有免疫学基础。胎儿滋养层上唯一已知的多态性组织相容性抗原是HLA-C分子。我们测试了这样一种观点，即母体蜕膜NK细胞上的杀伤免疫球蛋白受体（KIR）对这些分子的识别是先兆子痫发生的关键因素。引人注目的差异时，观察到这些多态性配体：受体对被认为是在组合。当胎儿具有属于HLA-C2组的HLA-C时，缺乏大部分或全部活化KIR（AA基因型）的母亲患先兆子痫的风险大大增加。即使母亲自己也有HLA-C2，这也是正确的，这表明非我或缺失自我的歧视都不起作用。因此，母体KIR和滋养层之间的这种相互作用似乎不具有免疫功能，而是发挥与胎盘发育相关的生理作用。不同的人群之间的AA频率和HLA-C2频率的相互关系，这表明对这种组合的选择。根据我们的研究结果，生殖成功可能是人类HLA-C和KIR多态性进化和维持的一个因素。
Preeclampsia is a serious complication of pregnancy in which the fetus receives an inadequate supply of blood due to failure of trophoblast invasion. There is evidence that the condition has an immunological basis. The only known polymorphic histocompatibility antigens on the fetal trophoblast are HLA-C molecules. We tested the idea that recognition of these molecules by killer immunoglobulin receptors (KIRs) on maternal decidual NK cells is a key factor in the development of preeclampsia. Striking differences were observed when these polymorphic ligand: receptor pairs were considered in combination. Mothers lacking most or all activating KIR (AA genotype) when the fetus possessed HLA-C belonging to the HLA-C2 group were at a greatly increased risk of preeclampsia. This was true even if the mother herself also had HLA-C2, indicating that neither nonself nor missing-self discrimination was operative. Thus, this interaction between maternal KIR and trophoblast appears not to have an immune function, but instead plays a physiological role related to placental development. Different human populations have a reciprocal relationship between AA frequency and HLA-C2 frequency, suggesting selection against this combination. In light of our findings, reproductive success may have been a factor in the evolution and maintenance of human HLA-C and KIR polymorphisms.
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影响因子：
20.3
作者：
Cook, MA;Milligan, DW;Briggs, DC
通讯作者：
Briggs, DC
影响因子：
--
作者：
Crum, KA;Logue, SE;Middleton, D
通讯作者：
Middleton, D
影响因子：
4.4
作者：
Gonen-Gross, T;Achdout, H;Mandelboim, O
通讯作者：
Mandelboim, O
DOI：
10.1016/s0020-7292(97)00241-5
发表时间：
1998-01-01
影响因子：
3.8
作者：
Cincotta, RB;Brennecke, SP
通讯作者：
Brennecke, SP
DOI：
10.1073/pnas.90.24.12000
发表时间：
1993-12-15
影响因子：
11.1
作者：
COLONNA, M;BORSELLINO, G;STROMINGER, JL
通讯作者：
STROMINGER, JL