The Expression Of HLA-G Proteins By The Placental Cells In Preeclampsia

Pre-eclampsia, one of the main complications in pregnancy charact- erized by pregnancy-induced hypertension , oedema and proteinuria .It affects 7-12% of all pregnancies with varying severity and is a leading cause of maternal and fetal mortality. The aetiology is still un-clean,and it is thought to result from the immunological maladaptation,a poor perfusion of placenta,vascular endothelial cell dysfunction and genetic predisposition. From the early study of the pathogenesis of pre-eclampsia people have found its association with immunological function . In 1986 Ellis et al[1] had found that the extravillous chorionic cytotrophoblast contacting with the maternal tissue expressed high levels of Human leukocyte antigen (HLA)-G, a major histocompatibility tissue-specific antigen . Extravillous chorionic cytotrophoblast with high levels expression of HLA-G proteins can invade the maternal deciduas and the maternal spiral arteries by displacing the endothelial lining and destroying most of the musculoelastic tissue of these arteries . So it is supposed that HLA-G protein can be a key molecule in maternal-fetal tolerance. HLA-G is in the distant of the human MHC on the short arm of chromosome 6 ,including 8 extrons and 7 introns .A feature unique to HLA-G, a nonclassical HLA class I locus, is alternative splicing of its primary transcript, resulting in at least six isoforms: four membrane-bound proteins (HLA-G1 to HLA-G4) and two soluble proteins (HLA-G5 and -G6).They play important rolls on immune tolerance.Objective: Through immunohistochemical method, we studied the expression pattern of HLA-G proteins in normal pregnant placenta and placenta from pregnancies complicated by pre-eclampsia, furthermore , todemonstrate the function and the value of HLA-G protains .Materials and methods: Ninety- five placental cases (the study group)from the pre-eclamptic patients and thirty placental cases (the control group)from the normal pregnant women with uncomplicated pregnancies and with no pregnancy medical problems were collected in this study. The pre-eclamptic patients were divided into 2 groups: light pre-eclamptic patients group ( n = 30) and severe pre-eclamptic patients group ( n = 65). The severe pre-eclamptic patients were divided into 2 groups: early onset group ( n = 30) with those onset≤34 weeks of gestation and late onset group ( n = 35)with onset > 34weeks of gestation .All the collections were regularily made into paraffin sections . The expression of HLA-G proteins of all the placental cases were detected by using immunohistochemical method (SP).Result: In normal placenta we found HLA-G proteins expression in the anchoring extravillous trophoblasts with an increasing gradient of expression in the more invasive cells. However, in pre-eclamptic placenta HLA-G proteins expression was absent or reduced characterized by island distribution .The placenta is divided into 4 grades according to the expression of HLA-G proteins . We use rank sum test to analyse the difference between the group of normal pregnancy and the group of pre-eclampsia(P=0.000) . We also use rank sum test to analyse the differe- nce between the light pre-eclampsia group and the severe pre-eclampsia group (P=0.000),the early onset pre-eclampsia group and the late onset pre-eclampsia group (P=0.003) . All of the results give the same conclude that the differences within the three groups are significant (P<0.05).Conclusion: We conclude that HLA-G proteins are normally expressed in invasive trophoblasts and HLA-G proteins expression is defective in most pre-eclamptic placenta.We propose that trophoblasts lacking HLA-G proteins are vulnerable to attack by the maternal immune system. These defective trophoblasts will be unable to invade the maternal spiral arteries effectively, thereby developing vessels which cannot adequately nourish the developing placenta. This poorly perfused placenta may initiate the systemic cascade of events associated with pre-eclampsia. Our work provides molecular evidence that this immune problem of pre-eclampsiamay be mediated by defective HLA-G proteins expression. We propose the dependability between the morbidity,severity,time and defective HLA-G proteins expression.