The development of preeclampsia in oocyte donation pregnancies is related to the number of fetal-maternal HLA class II mismatches

Bentem, Kim van; Bos, Manon; Keur, Carin van der; Brand-Schaaf, Simone H.; Haasnoot, Geert W.; Roelen, Dave L.; Eikmans, Michael; Heidt, Sebastiaan; Claas, Frans H.J.; Lashley, Eileen; Hoorn, Marie-Louise van der

doi:10.1016/j.jri.2019.103074

Cited by 18 publications

(17 citation statements)

References 39 publications

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“…Previous research showed that there is a selective advantage of HLA compatibility, to a similar degree as the one observed in naturally conceived pregnancies, in successful oocyte donation pregnancies ( 13 ). In addition, we found a strong relationship between the number of HLA class II mismatches and the occurrence of preeclampsia in oocyte donation pregnancies ( 14 ). Furthermore, we recently demonstrated that the total amount of HLA mismatches and that of HLA class I mismatches is associated with expression of immune modulatory molecules CD200 in uncomplicated oocyte donation pregnancies, suggestive of a higher compensatory need ( 15 ).…”

Section: Introductionmentioning

confidence: 82%

Maternal-Fetal HLA Compatibility in Uncomplicated and Preeclamptic Naturally Conceived Pregnancies

et al. 2021

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IntroductionIn 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.MethodsGenotyping 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).ResultsIn 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.ConclusionThe 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.

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Section: Introductionmentioning

confidence: 82%

Maternal-Fetal HLA Compatibility in Uncomplicated and Preeclamptic Naturally Conceived Pregnancies

et al. 2021

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“…42 However, while HLA antigen mismatches are observed to be associated with the development of preeclampsia in OD pregnancies, the influence of HLA antibodies on development of preeclampsia is uncertain. 40 The exact mechanism of how macrophages would respond to larger genetic dissimilarity is not yet clear and needs to be further established in the future. Macrophages possess abundant functions, including their interaction with and effect on other immune cells.…”

Section: Discussionmentioning

confidence: 99%

Uncomplicated oocyte donation pregnancies display an elevated CD163‐positive type 2 macrophage load in the decidua, which is associated with fetal‐maternal HLA mismatches

Tian

Aiyer

Kapsenberg

et al. 2021

American J Rep Immunol

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Problem: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. Method of study: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.Results: 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).Conclusions: 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.

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“…This process of fetal microchimerism evokes cellular and humoral immunity in the mother, involving both HLA class I‐ and class II‐specific immune components 98 . Furthermore, as far as HLA incompatibility between mother and child is concerned, we have found that the degree of HLA class II mismatching is related to clinical outcome in both autologous pregnancies 99 and oocyte donation pregnancies 100 . In addition, the number of HLA‐DR mismatches between mother and child determines the incidence of HLA class I specific alloantibodies in oocyte donation pregnancies 101 .…”

Section: Maternal T Cells and Myeloid Cells In The Placental Bedmentioning

confidence: 95%

“…98 Furthermore, as far as HLA incompatibility between mother and child is concerned, we have found that the degree of HLA class II mismatching is related to clinical outcome in both autologous pregnancies 99 and oocyte donation pregnancies. 100 In addition, the number of HLA-DR mismatches between mother and child determines the incidence of HLA class I specific alloantibodies in oocyte donation pregnancies. 101 Further studies should focus on unraveling the mechanisms behind the effect of maternal-fetal HLA class II mismatching on pregnancy outcome.…”

Section: Outstanding Issues Concerning Allogenicity and T Cell Reacmentioning

confidence: 99%

Got your mother in a whirl: The role of maternal T cells and myeloid cells in pregnancy

Eikmans

Zwan

Claas

et al. 2020

HLA

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Appropriate development of the placenta is required for healthy pregnancy to occur. After implantation of the fertilized blastocyst, fetal trophoblasts invade the endometrium and myometrium of the mother's uterus to establish placentation. In this process, fetal trophoblasts encounter maternal immune cells. In this review, we focus on the role of maternal T cells and myeloid cells (macrophages, dendritic cells) in pregnancy and their interaction with trophoblasts. To retain immunologic tolerization, trophoblasts evade immune recognition by T cells and produce factors that modulate their phenotype and function. On top of that, the local environment at the maternal‐fetal interface favors expansion of regulatory T cells. Macrophages and dendritic cells are essential in maintaining a healthy pregnancy. They produce soluble factors and act as antigen‐presenting cells, thereby interacting with T cells. Herein, M2 macrophages, immature dendritic cells, CD4+ Th2 cells, and regulatory T cells represent an axis that maintains a local immune tolerant environment. We consider outstanding issues concerning these cell types and their pathways, which need to be addressed in future investigations. Data from recent single‐cell sequencing experiments of the placental bed, to study heterogeneity of maternal immune cells and to predict cell‐cell interactions, are discussed. Novel ways for long‐term culturing of primary trophoblasts allow for cell‐cell interaction studies in a functional way. Future directions should include study of the functionality of currently known and newly identified decidual immune cell subsets in healthy and complicated pregnancies, and their interaction with and modulation by trophoblast cells.

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The development of preeclampsia in oocyte donation pregnancies is related to the number of fetal-maternal HLA class II mismatches

Cited by 18 publications

References 39 publications

Maternal-Fetal HLA Compatibility in Uncomplicated and Preeclamptic Naturally Conceived Pregnancies

Maternal-Fetal HLA Compatibility in Uncomplicated and Preeclamptic Naturally Conceived Pregnancies

Uncomplicated oocyte donation pregnancies display an elevated CD163‐positive type 2 macrophage load in the decidua, which is associated with fetal‐maternal HLA mismatches

Got your mother in a whirl: The role of maternal T cells and myeloid cells in pregnancy

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