Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, the Netherlands; Department of Gynecology and Obstetrics, Leiden University Medical Center, the Netherlands.
Department of Gynecology and Obstetrics, Leiden University Medical Center, the Netherlands; Department of Pathology, Leiden University Medical Center, the Netherlands.
J Reprod Immunol. 2020 Feb;137:103074. doi: 10.1016/j.jri.2019.103074. Epub 2019 Dec 5.
In oocyte donation (OD) pregnancy, a fetus can be completely allogeneic to the recipient. Consequently, the maternal immune system has to cope with greater immunogenetic dissimilarity compared to naturally conceived pregnancy. Previously, we showed an association between successful OD pregnancy and lower immunogenetic dissimilarity, reflected by the number of fetal-maternal Human Leukocyte Antigen (HLA) mismatches, than expected by chance. In this study we aimed to determine whether the development of preeclampsia in OD pregnancies is related to the number of fetal-maternal HLA mismatches. A retrospective, nested case-control study was performed within a cohort of 76 singleton OD pregnancies. Maternal and fetal umbilical cord blood was typed for HLA-A, -B, -C, -DR and -DQ, and the number of fetal-maternal HLA mismatches was calculated. In addition, the incidence of child-specific HLA antibodies was determined. 13 pregnancies were complicated by preeclampsia. To demonstrate an influence of HLA mismatches on the development of preeclampsia, a univariate logistic regression analysis was performed adjusted for maternal age and socio-economic status. A significant association between the number of fetal-maternal HLA class II mismatches and the development of preeclampsia was observed (OR = 3.8, 95 % CI: 1.6-9.0; p = 0.003). This association was not linked to the development of HLA class II antibodies. According to our findings, an increased number of HLA class II mismatches is a risk factor for the development of preeclampsia in OD pregnancies. The effect of HLA class II mismatches might be explained by the induction of a cellular rather than a humoral immune response.
在卵母细胞捐赠（OD）妊娠中，胎儿可以完全与受体异体。因此，与自然受孕妊娠相比，母体免疫系统必须应对更大的免疫遗传差异。此前，我们发现成功的 OD 妊娠与较低的免疫遗传差异相关，这反映在胎儿-母体人类白细胞抗原（HLA）错配数量上，低于预期的随机水平。在这项研究中，我们旨在确定 OD 妊娠中子痫前期的发展是否与胎儿-母体 HLA 错配数量有关。在 76 例单胎 OD 妊娠队列中进行了回顾性、嵌套病例对照研究。对母亲和胎儿脐带血进行 HLA-A、-B、-C、-DR 和-DQ 分型，并计算胎儿-母体 HLA 错配数量。此外，还确定了儿童特异性 HLA 抗体的发生率。13 例妊娠并发子痫前期。为了证明 HLA 错配对子痫前期发展的影响，进行了调整母亲年龄和社会经济地位的单变量逻辑回归分析。观察到胎儿-母体 HLA Ⅱ类错配数量与子痫前期发展之间存在显著相关性（OR=3.8，95%CI：1.6-9.0；p=0.003）。这种关联与 HLA Ⅱ类抗体的发展无关。根据我们的发现，增加 HLA Ⅱ类错配数量是 OD 妊娠中子痫前期发展的危险因素。HLA Ⅱ类错配的影响可能是由于诱导细胞免疫反应而不是体液免疫反应。
