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

Abstract

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.

The Mac Is Back: The Role of Macrophages in Human Healthy and Complicated Pregnancies

“…Additionally, a lower proliferative response by the maternal peripheral blood mononuclear cells to paired umbilical cord blood was found in OD pregnancies, compared with naturally conceived pregnancies [ 82 ]. Accordingly, OD pregnancies were investigated for the macrophage compartment, which demonstrate a higher CD163/CD14 ratio in the decidua parietalis than non-OD IVF pregnancies [ 83 ]. The OD cohort was then divided into a semi-allogeneic group (≤5 maternal-fetal HLA mismatches) and a fully allogeneic group (>5 mismatches): the HLA-fully-allogeneic OD group, but not the HLA-semi-allogeneic OD group, showed a significantly elevated CD163/CD14 ratio in the decidua parietalis compared with the non-OD IVF group [ 83 ].…”

“…Accordingly, OD pregnancies were investigated for the macrophage compartment, which demonstrate a higher CD163/CD14 ratio in the decidua parietalis than non-OD IVF pregnancies [ 83 ]. The OD cohort was then divided into a semi-allogeneic group (≤5 maternal-fetal HLA mismatches) and a fully allogeneic group (>5 mismatches): the HLA-fully-allogeneic OD group, but not the HLA-semi-allogeneic OD group, showed a significantly elevated CD163/CD14 ratio in the decidua parietalis compared with the non-OD IVF group [ 83 ]. Ongoing studies are focused on the spatial orientation of immune cells in situ to identify a possibly functional relationship between CD163+ macrophages and CD4+ T cells.…”