P–414 HLA-G expression as a new prognostic marker of successful implantation
Authors: Bakleicheva M , Bespalova O , Ivashchenko T , Tral T , Tolibova G 
Published: August 2021

Abstract

Study question
Is the low HLA-G expression a determinant of early reproductive loss?

Summary answer
Low expression of HLA-G is associated with pregnancy complications and can be one of the reasons of spontaneous abortion (such as RPL).

What is known already
The dysregulated maternal immune responses to invading embryos may play role in RIF, RPL, and second- and third-trimester obstetrical conditions. HLA-G is a molecule that was first known to confer protection to the fetus from destruction by the immune system of its mother, thus critically contributing to fetal–maternal tolerance due to inducing displacement of pro-inflammatory to Th1 cell-mediated response of Th2, has a positive influence on the process of implantation. HLA-G is mainly restricted to the fetal–maternal interface on the extravillous cytotrophoblast, to placenta, amnion.

Study design, size, duration
It was a prospective complex cohort study from 2016–2020 years with pathomorphological investigations. The purpose of this study is to investigate the HLA-G and KIR2DL4 expression in chorionic villous among 3 groups (study included 118 cases of abortion material): group 1 – 36 cases after missed abortion with normal karyotype, group 2 – 36 cases after missed abortion with polyploidy and group 3 – 46 cases after induced abortion group (normal pregnancy).

Participants/materials, setting, methods
Criteria of inclusion: abortive material from 3 groups of women with missed or after induced abortion; 6–12 weeks, singleton pregnancy, cytogenetic of chorionic villous was obligatorily - normal fetal karyotype and polyploidy of fetus. Pathomorophological investigation included H&E stain, IHC and confocal laser scanning microscopy. Immunohistochemical examination included quantitative and qualitative assessment of the expression of Anti-HLA-G (mouse monoclonal) in an extra villous trophoblast and Anti-KIR2DL1+KIR2DL3 + KIR2DL4 + KIR2DS4 (rabbit polyclonal) in chorionic villi.

Main results and the role of chance
The immunohistochemical study showed homogenous distribution HLA-G expression in extravillous trophoblast cells (EVT) and KIR2DL4 expression in chorion villous both in missed abortion groups and in induced abortion group. HLA-G expression average relative area in 1 and 2 groups was not statistically different (in 1 group with normal karyotype 33,9±3,5 and in 2 group 38,6±2,8). But the expression of HLA-G in 3 group was strictly higher (55,6 ±2,4). The average relative area of KIR2DL4 receptor wasn’t statistically different among 3 groups. However, the histological picture both missed abortion groups (for the genetic\immunological reasons for rejection) is the only one - this is a missed abortion of an early terms of gestation. In a histological study of missed abortion, as our study shows, the histological picture is similar in 1 and 2 groups. Thus, in 1 group with a normal karyotype of the fetus (before conducting the chorion cytogenetic study in the genetics laboratory) in 59.2% the histological examination determined a picture of an impaired early pregnancy with signs of trophoblast chromosomal pathology. Thus, without a cytogenetic study of the chorion, it is impossible to clearly determine whether the chromosomal pathology of the fetus is the cause of missed abortion.

Limitations, reasons for caution
There is no limitations, reasons for caution.
Wider implications of the findings: Thus, HLA-G molecule has a leading role in the onset and successful prolongation of pregnancy, implantation, placentation and fetal development.

Trial registration number
98–2019