Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, Netherlands.
Department of Immunology, Leiden University Medical Center, Leiden, Netherlands.
Am J Reprod Immunol. 2022 Jan;87(1):e13511. doi: 10.1111/aji.13511. Epub 2021 Dec 4.
The embryo of an oocyte donation (OD) pregnancy is completely allogeneic to the mother, which may challenge the maternal immune system to tolerize the fetus. Decidual macrophages are essential in maintaining a healthy pregnancy, and type 2 macrophages may exhibit immune suppressive activity. We hypothesized that the composition of decidual macrophages is different between uncomplicated OD pregnancies and non-OD in vitro fertilization (IVF) pregnancies, and is related to fetal-maternal incompatibility.
Women with uncomplicated pregnancy were enrolled: 25 singleton OD pregnancies and 17 non-OD IVF pregnancies. The extent of immunohistochemical staining of CD14 (pan-macrophage marker) and CD163 (type 2 macrophage marker) in both decidua basalis and parietalis was quantitated by digital image analysis. Maternal and fetal DNA was typed for human leukocyte antigen (HLA)-A, -B, C, -DRB1, and -DQB1, and fetal-maternal HLA mismatches were calculated.
OD pregnancies showed a higher percentage of CD163+ staining (P = .040) and higher CD163/CD14 ratio (P = .032) in the parietalis than non-OD IVF. The OD group was separated into a semi-allogeneic group (≤5 fetal maternal HLA mismatches) and a fully allogeneic group (> 5 mismatches). The HLA-fully-allogeneic OD group, but not the HLA-semi-allogeneic OD group, showed significantly elevated CD163/CD14 ratio in the parietalis compared with the non-OD IVF group (P < .05).
Uncomplicated OD pregnancies display a higher CD163-positive cell fraction in the total decidual macrophage population compared to autologous pregnancies, which may suggest that a local type 2 macrophage-related mechanism is needed to compensate for the higher fetal-maternal HLA mismatch load.
卵母细胞捐赠(OD)妊娠的胚胎与母亲完全异体,这可能会挑战母体免疫系统使胎儿耐受。蜕膜巨噬细胞对于维持健康妊娠至关重要,而 2 型巨噬细胞可能具有免疫抑制活性。我们假设,在单纯 OD 妊娠和非 OD 体外受精(IVF)妊娠中,蜕膜巨噬细胞的组成不同,并且与胎儿-母体不相容有关。
入组了具有单纯妊娠的女性:25 例单胎 OD 妊娠和 17 例非 OD IVF 妊娠。通过数字图像分析定量测定蜕膜基底和壁部的 CD14(巨噬细胞通用标志物)和 CD163(2 型巨噬细胞标志物)免疫组织化学染色的程度。对母胎 DNA 进行人白细胞抗原(HLA)-A、-B、-C、-DRB1 和 -DQB1 分型,并计算胎儿-母体 HLA 错配。
OD 妊娠的壁部 CD163+染色百分比(P=.040)和 CD163/CD14 比值(P=.032)高于非 OD IVF。OD 组分为半同种异体组(≤5 个胎儿-母体 HLA 错配)和完全同种异体组(>5 个错配)。与非 OD IVF 组相比,仅 HLA 完全同种异体 OD 组,而非 HLA 半同种异体 OD 组的壁部 CD163/CD14 比值显著升高(P<.05)。
与自体妊娠相比,单纯 OD 妊娠的总蜕膜巨噬细胞群体中 CD163 阳性细胞比例较高,这可能表明需要局部 2 型巨噬细胞相关机制来补偿较高的胎儿-母体 HLA 错配负荷。