Expression And Clinical Significance Of HLA-G And HLA-E In Placentas From Women With Preeclampsia

Preeclampsia is a specific disease during pregnancy, is characterized by hypertension, proteinuria, and other systemic disorders, is one of the main reasons of leading to maternal and perinatal disease and mortality, and seriously threatens maternal and child health. So far, there are a variety of theories about the causes and pathogenesis of preeclampsia, but these theories are not fully clarified. Pregnancy is considered to be successful natural allograft. Immune tolerance is the key to successful pregnancy, the reason why the fetus is not excluded from mother during pregnancy is the immune barrier function of the placenta. Extravillous cytotrophoblast (EVCT) on the maternal-fetal interface is the fetal-derived ingredient which is directly in contact with mother's body, it does not express classical human leukocyte antigen (HLA) I class and II class molecules, but it specifically expresses non-classical HLA-I class molecule HLA-G, E, F, this unique tissue distribution plays a crucial role in the maternal-fetal immune tolerance.HLA-G and E are very important immune tolerance molecules, all belong to non-classical HLA-I molecules, and are located on the human No. 6 chromosome short arm. In 1987, Geraghty and so on firstly cloned HLA-G genes successfully, HLA-G molecules have three main features: 1) restricted tissue distribution, HLA-G restricted expression is on the EVCT of maternal-fetal interface; 2) low polymorphism feature, HLA-G gene polymorphism is far less than the classical HLA-I genes, at present, found HLA-G alleles are 16; 3) mRNA alternative splicing, primary transcript of HLA-G gene generates different mRNA subtypes after alternative splicing, the subtypes are translated into seven kinds of protein isomers, wherein 4 kinds are membrane bound molecules (mHLA-G), and 3 kinds are soluble molecules (sHLA-G). At present, scholars have generally agreed that HLA-G protein is mainly high expressed on EVCT of maternal-fetal interface, the unique organization distribution has very important role for maintenance of normal pregnancy. HLA-G not only is an antigen-presenting molecule, but also can induce maternal-fetal immune tolerance through a variety of mechanisms, and it mainly adjusts immunologically competent cells in decidual tissues. HLA-G molecules can inhibit cell lysis of NK cells and T cells, induce CD8+T lymphocyte apoptosis, and adjust cytokine release, thereby affecting the body's immune response. Therefore, abnormal expression of HLA-G molecules can cause infertility, habitual abortion, pregnancy hypertension and other pathological pregnancy. At present, research on HLA-G in pregnancy is wider, however the research on expression conditions and action mechanism of HLA-E expression in pregnancy is relatively lacking. HLA-E is a non-classical HLA-I gene which was identified in 1988 by the Koller. HLA-E and HLA-G have the same expression position, namely, it is also expressed on EVCT of maternal-fetal interface because peptide binding grooves of HLA-E can be expressed on the surface of cells after peptide specific binding with leader sequences derived from classical HLA-I molecules (HLA-Ia), or HLA- G molecules. HLA-E molecules also have three main characteristics: 1) extensive tissue distribution, HLA-E is the only module which has mRNA transcription in all human tissue cells thus far; 2) limited polymorphisms, HLA-E is a quite conservative non-classical HLA-I molecule, its allele has limited polymorphism, at present, alleles which are named by the World Health Organization are only six; 3) low level of expression, HLA-E molecules show extremely low cell surface expression in most human tissues, in early pregnancy, HLA-E is weakly expressed in the surface or cytoplasm of extravillous trophoblast cells, the expression is increased gradually in mid-pregnancy. HLA-E molecules also can act with NK cells mutually to adjust maternal-fetal immune tolerance. This study discusses the function and clinical significance of HLA-G in preeclampsia pathogenesis through detecting the expression condition of HLA-G in placentas of normal pregnant women and preeclampsia patients. The experiment collects preeclampsia patients (30 mild patients and 30 severe patients) and normal pregnant women (30 cases) from the Second Hospital of Jilin University, and adopts immunohistochemistry to detect the expression condition of HLA-G, E molecules in placenta tissues. Experimental data apply statistical software SPSS13.0 for statistical analysis, comparison among the groups adopts One-way ANOVA, and correlation analysis adopts Pearson correlation test.Experimental results show that: HLA-G, E molecules have brown positive staining particle expression in placenta tissue extravillous trophoblast cells and the cell membrane and cytoplasm of EVCT, corresponding nuclei are blue, wherein EVCT is the main expression site. The average absorbance values of HLA-G, E molecules in normal pregnant group are: 23247.83±4614.04 and 24443.60±5537.09, the average absorbance values in the mild preeclampsia group are: 18624.13±4541.10 and 19748.63±5133.55 and the average absorbance values in severe preeclampsia group are: 14338.73±4302.09 and 14827.63±5359.61. The expression of HLA-G, E molecules in preeclampsia group is significantly lower than that in the normal pregnancy group, the difference is statistically significant (P<0.05); the expression in severe preeclampsia group is significantly lower than that in the mild preeclampsia group, and the difference is statistically significant (P<0.05). The expression of HLA-G, E molecules in placental tissues of normal pregnant women, mild preeclampsia patients and severe preeclampsia patients is gradually decreased, and the expressions of them in each group show positive correlation.In summary, the following conclusions can be obtained: HLA-G, E molecules show high level expression in placenta tissues of normal pregnant women and may be involved in adjusting normal pregnancy maternal-fetal immune tolerance; the HLA-G, E molecules show low level expression in placenta tissues of preeclampsia patients and may be related with the pathogenesis of preeclampsia; the expression in placenta tissues of severe preeclampsia patients is significantly lower than that in patients with mild preeclampsia, indicating that it may have negative correlation with the severity of disease. The expression of HLA-G and HLA-E in placenta tissues of normal pregnant women, mild preeclampsia patients and severe preeclampsia patients shows positive correlation, which suggests they may have accompanying expression relation. HLA-G, E molecules play an important role in the mechanism of maternal-fetal immune regulation, and in-depth understanding of expression and significance of HLA-G, E molecules in the placenta tissues has important value for elucidating fetal immune tolerance mechanisms, and provides a new way of thinking for diagnosis and treatment of preeclampsia at the same time.