Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, OX3 9DU, UK; Department of Woman and Child Health, Fondazione Policlinico A. Gemelli IRCCS, L.go A. Gemelli 8 00168, Rome, Italy.
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, OX3 9DU, UK.
J Reprod Immunol. 2018 Sep;129:48-52. doi: 10.1016/j.jri.2018.06.024. Epub 2018 Jun 19.
In normal pregnancy, villous cytotrophoblast and syncytiotrophoblast do not express HLA Class I and Class II molecules, while invasive extravillous trophoblast only express class I HLA-C and the atypical class Ib antigens, HLA-G, -E and -F. Inadequate maternal tolerance of invasive trophoblast has been proposed as a possible immunologic trigger of poor trophoblast invasion and subsequent occurrence of pre-eclampsia. This study aimed to investigate possible aberrant expression of class II HLA-DR on placentae and syncytiotrophoblast-derived extracellular vesicles (STEVs), obtained by dual placental perfusion, from pre-eclampsia (n = 23) and normal pregnant (n = 14) women. Here we demonstrate that HLA-DR can be detected in syncytiotrophoblast from a significant proportion of pre-eclampsia but not control placentae. HLA-DR was also observed, by flow cytometry, on STEVs and associated with placental alkaline phosphatase to validate their placental origin. HLA-DR positive syncytiotrophoblast was detected in placental biopsies from pre-eclampsia but not normal control cases, using immunohistochemistry. The HLA may be fetal or maternal origin. In the latter case a possible mechanism of acquisition is trogocytosis.
在正常妊娠中,绒毛滋养层细胞和合体滋养层细胞不表达 HLA Ⅰ类和Ⅱ类分子,而浸润性绒毛外滋养层仅表达Ⅰ类 HLA-C 和非典型的 Ib 类抗原 HLA-G、-E 和 -F。有人提出,母体对浸润性滋养层的耐受性不足可能是导致滋养层浸润不良和随后发生子痫前期的免疫触发因素。本研究旨在探讨子痫前期(n=23)和正常妊娠(n=14)妇女通过双胎盘灌注获得的胎盘和合体滋养层衍生的细胞外囊泡(STEVs)上 HLA-DR 类Ⅱ分子是否存在异常表达。本研究结果表明,在相当一部分子痫前期患者的合体滋养层中可以检测到 HLA-DR,但在对照组胎盘组织中则不能。通过流式细胞术还观察到 HLA-DR 存在于 STEVs 上,并与胎盘碱性磷酸酶相关联,以验证其胎盘来源。使用免疫组织化学法在子痫前期的胎盘活检中检测到 HLA-DR 阳性的合体滋养层,但在正常对照组中则没有。HLA 可能来自胎儿或母体,如果是后者,其获得的可能机制是 trogocytosis。