P-398 HLA expression profile - the picture of successful pregnancy
Authors: Bakleicheva M , Bespalova O , Ivashchenko T , Tral T , Tolibova G , Tikhonov A , Petrova L , Dudkina V 
Published: June 2022

Abstract

Study question
Which the difference of HLA profile expression among normal and abnormal karyotype?

Summary answer
In missed abortion groups, a significant decrease in HLA-G expression is observed in the chorionic villus structures in comparison with normal karyotype group.

What is known already
The study of pregnant alloimmunity confirms the relationship of recurrent miscarriage with the individual characteristics of the HLA I and II class system (Human leukocyte antigen), which can lead to impaired production of the mixed lymphocyte reaction blocking antibodies (MLR-Bf), anti-paternalcyto-toxicantibodies (APCA) and anti-idiotypic antibodies, Ab2, which are necessary for successful implantation and pregnancy development. For example, HLA-G is mainly restricted to the fetal–maternal interface on the extravillous cytotrophoblast, to placenta, amnion when HLA II class system mostly determinates in dNK, T-cells, macrophages.

Study design, size, duration
It was a prospective complex cohort study from 2016-2020 years with cytogenetics and pathomorphological investigations. The purpose of this study is to investigate HLA-DR expression in gravid endometrium, HLA-G and KIR2DL4 expression in chorionic villous among 3 groups (study included 115 cases of abortion material): group 1 – 36 cases after missed abortion with normal karyotype, group 2–35 cases after missed abortion with polyploidy and group 3–44 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. In this work, we used: cytogenetic method and morphological study (histological-H&E stain, immunohistochemical, morphometric method). Immunohistochemical examination included quantitative and qualitative assessment of the expression of Anti-HLA-DR (mouse monoclonal), Anti-HLA-G (mouse monoclonal) and AntiKIR2DL1+KIR2DL3 + KIR2DL4 + KIR2DS4 (rabbit polyclonal).

Main results and the role of chance
By IHC the expression of HLA-G in extravillous trophoblast cells but the expression of HLA-DR and KIR2DL4 were detected in stroma, glands, the endometrial epithelium, both in groups.The HLA-G expression area in both groups with missed abortion didn’t differ statistically. But the expression of HLA-G in 3 group was strictly higher (in group 1 with a normal karyotype 37.7, in group 2-36.4, in the control group 67.09, p &lt; 0.001). When divided into subgroups depending on the karyotype, the following data were obtained: in the group with a non-developing pregnancy with a normal karyotype of male fetuses, there is a tendency to lower expression of HLA-G molecules compared to female fetuses (32.96 (10.22) and 41 .45(9.36), respectively). Expression of the KIR2DL4 receptor was verified in chorionic villi (in the cytotrophoblast and syncytiotrophoblast), as well as in the structures of the endometrium, both in the glands, stroma, and in the surface epithelium, regardless of the karyotype. The expression area of the KIR2DL4 receptor did not differ statistically between the three groups (29.6, 33.1 and 27.55, p = 0.75). The expression area of the HLA-DR was detected in each group in gravid endometrium, but it hadn’t statistically differences (44.1, 38.2 and 42.5, p = 0.82).

Limitations, reasons for caution
No reasons for cautions

Wider implications of the findings
In missed abortion groups,a significant decrease in HLA-G expression is observed in the chorionic villus structures in comparison with the control group.The mechanism of abortion in groups with missed abortion with both normal karyotype and pathological karyotype of the fetus is identical.HLA-G molecule has a leading role in successful implantation.

Trial registration number
АААА-А20-120041390025-9