HLA-DR is aberrantly expressed at feto-maternal interface in pre-eclampsia

Area of Science:

• Immunology
• Reproductive Biology
• Perinatology

Background:

• Normal pregnancy involves specific Human Leukocyte Antigen (HLA) expression patterns on trophoblast cells.
• Invasive extravillous trophoblast expresses HLA Class I (HLA-C) and atypical Class Ib antigens (HLA-G, -E, -F).
• Aberrant maternal immune tolerance to trophoblast is implicated in pre-eclampsia due to poor trophoblast invasion.

Purpose of the Study:

• To investigate the expression of Human Leukocyte Antigen - Antigen D Related (HLA-DR) in placentae and syncytiotrophoblast-derived extracellular vesicles (STEVs) from women with pre-eclampsia and normal pregnancies.
• To determine if HLA-DR expression differs between pre-eclamptic and normal placentae and STEVs.

Main Methods:

• Dual placental perfusion was used to obtain syncytiotrophoblast-derived extracellular vesicles (STEVs).
• Immunohistochemistry was employed to detect HLA-DR positive syncytiotrophoblast in placental biopsies.
• Flow cytometry was used to analyze HLA-DR expression on STEVs, validated by association with placental alkaline phosphatase.

Main Results:

• HLA-DR was detected in the syncytiotrophoblast of placentae from a significant proportion of pre-eclampsia cases, but not in control placentae.
• HLA-DR was also identified on STEVs from pre-eclamptic pregnancies.
• Immunohistochemistry confirmed HLA-DR positive syncytiotrophoblast in pre-eclampsia placental biopsies, absent in normal controls.

Conclusions:

• Aberrant expression of HLA-DR in syncytiotrophoblast and STEVs is associated with pre-eclampsia.
• The origin of HLA-DR (fetal or maternal) requires further investigation, with trogocytosis proposed as a maternal acquisition mechanism.
• These findings suggest a potential immunological basis for pre-eclampsia involving HLA-DR dysregulation.