Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway.
Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
HLA. 2024 Oct;104(4):e15717. doi: 10.1111/tan.15717.
Foetal cells are detectable in women decades postpartum, a state termed foetal microchimerism. The interplay between these semi-allogeneic foetal cells and the mother could be affected by genetic mismatches in the HLA loci. Here, we relate HLA allele and molecular mismatch values to the presence and quantity of foetal microchimerism in the maternal circulation during pregnancy and postpartum. A total of 76 pregnant women were included, of which 59 were followed up 1-8 years postpartum. Maternal and foetal DNA was genotyped for HLA class I and II loci. Foetal cells in maternal buffy coat were detected by qPCR, targeting inherited paternal alleles. Antibody-verified eplet mismatch and Predicted Indirectly Recognisable HLA Epitopes (PIRCHE) scores were calculated to quantify foetal-maternal histocompatibility from the mother's perspective. Circulating foetal cells were detected in 50.0% (38/76) of women during pregnancy, and 25.4% (15/59) postpartum. During pregnancy, HLA class II antibody-verified eplet mismatch load and PIRCHE scores correlated negatively with the presence and quantity of foetal cells in the maternal circulation. Postpartum, HLA class I allele mismatches correlated negatively with foetal microchimerism presence, while HLA class II allele mismatches, HLA class I and II antibody-verified eplet mismatch load, and PIRCHE-I and PIRCHE-II scores correlated negatively with both microchimerism presence and quantity. The correlation between mismatch parameters aimed at evaluating the risk of humoral and T cell-mediated allorecognition and foetal microchimerism was more evident postpartum than during pregnancy. The observed predictive effect of foetal-maternal histocompatibility on foetal microchimerism suggests that circulating foetal cells are subject to clearance by the maternal immune system. We propose that allorecognition of foetal cells in the maternal circulation and tissues influences any long-term effect that foetal microchimerism may have on maternal health.
胎儿细胞在产后数十年的女性中可检测到，这种状态被称为胎儿微嵌合体。这些半同种异体胎儿细胞与母亲之间的相互作用可能受到 HLA 基因座遗传不匹配的影响。在这里，我们将 HLA 等位基因和分子不匹配值与怀孕期间和产后母亲循环中胎儿微嵌合体的存在和数量相关联。总共纳入了 76 名孕妇，其中 59 名在产后 1-8 年进行了随访。对母亲和胎儿的 DNA 进行了 HLA Ⅰ类和Ⅱ类基因座的基因分型。通过 qPCR 检测母体白细胞中的胎儿细胞，以靶向遗传的父系等位基因。从母亲的角度计算抗体验证的 eplet 不匹配和预测间接可识别 HLA 表位 (PIRCHE) 评分，以量化胎儿-母体组织相容性。在怀孕期间，50.0%（38/76）的女性中检测到循环胎儿细胞，25.4%（15/59）的女性在产后检测到。在怀孕期间，HLA Ⅱ类抗体验证的 eplet 不匹配负荷和 PIRCHE 评分与母体循环中胎儿细胞的存在和数量呈负相关。产后，HLA Ⅰ类等位基因不匹配与胎儿微嵌合体的存在呈负相关，而 HLA Ⅱ类等位基因不匹配、HLA Ⅰ类和Ⅱ类抗体验证的 eplet 不匹配负荷以及 PIRCHE-I 和 PIRCHE-II 评分与微嵌合体的存在和数量均呈负相关。旨在评估体液和 T 细胞介导的同种异体识别和胎儿微嵌合体风险的不匹配参数之间的相关性，在产后比怀孕期间更为明显。胎儿-母体组织相容性对胎儿微嵌合体的观察预测作用表明，循环胎儿细胞易被母体免疫系统清除。我们提出，母体循环和组织中胎儿细胞的同种异体识别影响胎儿微嵌合体可能对母体健康产生的任何长期影响。
