HLA-G 14 bp Polymorphism and Risk of Pre-Eclampsia

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Pre-eclampsia belongs to one of very serious complication during pregnancy. It is a multisystem disorder that is manifested by hypertension, proteinuria and abnormal blood clotting. Advanced clinical symptoms include seizures, renal failure, IUGR (Intrauterine Growth Restriction) and/or HELLP (Hemolysis, Elevated Liver Enzymes and Low Platelets) syndrome. Finally the generalized damage of the maternal endothelium, kidneys and liver can develop leading to increased mortality of mother as well as foetus. The clinical symptoms of pre-eclampsia can be observed in the second or the third trimester in pregnancy and are the most common in primiparas. Clinical features of PE are studied by Doppler flowmetry not only in foetal and foetoplacental circulation as well as in maternal organs, i.e. uterine  cerebral ophthalmic and renal vessels. Stiffness metabolic syndrome and risk of CVD are other clinical research topics.

Despite many research studies, the pathology of pre-eclampsia is not fully understood. One cause may originate in an insufficiently developed placenta, referred to as poor placentation. It is characterized by impaired remodeling of spiral arteries of the uterus (endothelial dysfunction) caused by an imbalance of circulating angiogenic factors. High circulating levels of soluble Fms like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), a circulating receptor or TGFbeta, (both anti-angiogenic factors) and low levels of circulating Vascular Endothelial Growth Factor (VEGF) and Placental Growth Factor (PlGF) (both pro-angiogenic factors) have been described.

There are also immunological factors that can induce pregnancy disorders including pre-eclampsia. One of the immune molecules that play a beneficial role in the pregnancy is the Human Leukocyte Antigen G (HLA-G). HLA-G is a non-classical HLA class I protein that exerts various immunosuppressive functions. The molecule is mainly expressed on trophoblast cells in the foetal placenta and induces the immune tolerance of foetus. Immunosuppressive activity of HLA-G molecule is mediated through its interaction with inhibitory receptors of immune cells: ILT-2 present on B, APC and some T, NK cells, ILT-4 on APC and KIR2DL4 expressed by NK and some T cells. Thus HLA-G mediates inhibition of cytotoxic activity of uterine and peripheral blood NK cells and CD8⁺ T cells, inhibition of all proliferative response of CD4+ T cells; inhibition of Dendritic cells maturation and activates regulatory T cells.