P-420 Pre-selected for an award: Uncomplicated oocyte donation pregnancies display elevated CD163 positive type 2 macrophage load in the decidua, which is associated with fetal-maternal HLA class II mismatches
Authors: Tian X , Aiyer K T S , Kapsenberg H M , Roelen D L , Hoorn M L V D , Eikmans M 
Published: August 2021

Abstract

Study question
Do quantity and composition of decidual macrophages differ between uncomplicated oocyte donation (OD) pregnancies and non-OD in vitro fertilization (IVF) pregnancies?

Summary answer
OD placentas show higher decidual CD163 positive fraction within the total macrophage population compared to non-OD IVF placentas.

What is known already
The embryo of an OD pregnancy is completely allogeneic to the mother, which may lead to a bigger challenge for the maternal immune system to tolerize the fetus compared to autologous pregnancies. Placental macrophages may be essential in maintaining a healthy pregnancy. Macrophages can be classified into different categories based on phenotype and characteristics, in which type 2 macrophages are thought to exhibit immune suppressive activity.

Study design, size, duration
This retrospective case-control study included patients who delivered in the Leiden University Medical Center between January 1st 2006 and July 1st 2016. A total of 42 pregnancies were enrolled in this study, conceived by uncomplicated singleton OD pregnancies (n = 25) or non-OD IVF pregnancies (n = 17). Medical records were reviewed and clinical data were collected. Placental tissue samples were collected for immunohistochemical staining and blood samples were collected for HLA typing.

Participants/materials, setting, methods
Placentas were collected and immunohistochemically stained for CD14 (pan-macrophage marker) and CD163 (type 2 macrophage marker). The extent of staining was quantitated by digital image analysis software. To assess mismatching, maternal and fetal DNA was typed for HLA-A, -B, C, -DRB1, and -DQB1.

Main results and the role of chance
A significantly lower percentage of CD14 positive staining was observed in the decidua basalis of OD pregnancies compared to non-OD IVF pregnancies (p = 0.030). Consequently, the CD163/CD14 ratio in OD group was higher than in non-OD IVF group (p = 0.243). In the parietalis, OD pregnancies demonstrated a significantly higher percentage of CD163+ staining (p = 0.040) and a significantly higher CD163/CD14 ratio (p = 0.032) compared to non-OD IVF group. The reproducibility of this quantitative analysis was found to be high. OD group was separated into a syngeneic group (number of mismatches lower than half of the antigens per HLA locus) and an allogeneic group (number of mismatches higher than half of the antigens per HLA locus). Significant differences of CD163+ and CD163/CD14 ratio were found in the decidua parietalis when comparing the HLA-classII-allogeneic OD group with the non-OD IVF group (p = 0.047). This difference was not found for the HLA-class-II-syngeneic OD group.

Limitations, reasons for caution
Our study only focused on decidua basalis and parietalis, no other locations in the placentas. Larger sample size might be needed to verify the association between macrophages and HLA mismatches.

Wider implications of the findings
To our knowledge, this study is the first to quantify a higher CD163 positive M2 macrophages load within the total decidual macrophages of uncomplicated OD pregnancy compared to non-OD IVF pregnancies.

Trial registration number
not applicable