Department of Obstetrics and Gynaecology, Leiden University Medical Center, Leiden, Netherlands.
Department of Immunology, Leiden University Medical Center, Leiden, Netherlands.
Front Immunol. 2021 May 13;12:673131. doi: 10.3389/fimmu.2021.673131. eCollection 2021.
In pregnancy, the mother and fetus differ in HLA antigens, and yet the maternal immune system generally tolerates the fetus. KIR receptors expressed by maternal uterine NK cells at the maternal-fetal interface directly interact with HLA-C on extravillous trophoblast cells for optimal placental development. In this study, we aimed to determine whether there is a preferential selection for HLA compatibility and specific KIR/HLA-C combinations in uncomplicated and preeclamptic naturally conceived pregnancies compared to what would be expected by chance.
Genotyping for maternal and fetal HLA-A, -B, -C, -DR, and -DQ, and maternal KIR was performed for 451 uncomplicated pregnancies and 77 pregnancies complicated with preeclampsia. The number of HLA antigen (mis)matches between mother and fetus was calculated and compared to expected values obtained by randomization of the HLA haplotype, inherited from the father, over the existing maternal haplotype of the fetuses. A similar methodology was executed for analysis of the KIR/HLA-C data (n=309).
In uncomplicated pregnancies, the degree of maternal-fetal HLA matching was not different than expected-by-chance values. In preeclamptic pregnancies, the degree of maternal-fetal HLA matching was different in observed compared to expected-by-chance values (p=0.012). More specifically, the degree of maternal-fetal matching of HLA-C was higher in the actual preeclamptic pregnancies than was expected-by-chance (p=0.007). Preeclamptic pregnancies showed an overall tendency towards higher maternal-fetal HLA compatibility, for total HLA matches (p=0.021), HLA class I (p=0.038) and HLA-C (p=0.025) compared to uncomplicated pregnancies.
The data suggest that there is no preferential selection of maternal-fetal HLA compatibility in uncomplicated pregnancies. In contrast, increased total HLA, HLA class I and, especially, HLA-C compatibility is associated with preeclampsia, suggestive for a role of HLA mismatches in immune regulation leading to uncomplicated pregnancy.
在妊娠期间，母亲和胎儿的 HLA 抗原存在差异，但母体免疫系统通常能耐受胎儿。母体子宫 NK 细胞在母体-胎儿界面表达的 KIR 受体直接与绒毛外滋养层细胞上的 HLA-C 相互作用，以促进胎盘的最佳发育。在这项研究中，我们旨在确定与无并发症和子痫前期自然受孕妊娠相比，HLA 相容性和特定 KIR/HLA-C 组合是否存在优先选择，而这与随机选择的结果相反。
对 451 例无并发症妊娠和 77 例子痫前期妊娠的母亲和胎儿 HLA-A、-B、-C、-DR 和 -DQ 以及母亲 KIR 进行基因分型。计算母亲和胎儿之间 HLA 抗原（错）匹配的数量，并与通过从父亲遗传的 HLA 单倍型随机化到现有胎儿母体单倍型获得的预期值进行比较。对 KIR/HLA-C 数据（n=309）进行了类似的分析。
在无并发症的妊娠中，母亲与胎儿的 HLA 匹配程度与随机值无差异。在子痫前期妊娠中，观察到的母亲与胎儿的 HLA 匹配程度与随机值不同（p=0.012）。更具体地说，与预期值相比，实际子痫前期妊娠中 HLA-C 的母亲与胎儿的匹配程度更高（p=0.007）。与无并发症妊娠相比，子痫前期妊娠总体上存在更高的母婴 HLA 相容性，总 HLA 匹配（p=0.021）、HLA Ⅰ类（p=0.038）和 HLA-C（p=0.025）。
数据表明，无并发症妊娠中不存在母体与胎儿 HLA 相容性的优先选择。相反，增加的总 HLA、HLA Ⅰ类，特别是 HLA-C 相容性与子痫前期相关，提示 HLA 错配在免疫调节中起作用，导致无并发症妊娠。
