Study Of The Relationship Between CD28 And CTLA-4 Disturbance Of Peripheral And Decidual Lymphocytes And Preeclampsia

Normal pregnancy relies on the establishment and stabilization of maternal-fetal immunity balance,which once imbalance,it will cause pathology pregnancy.Hypertensive disorders complicating pregnancy is typical disease in the gestation,but preeclampsia is a kind of development phase,even eclampsiao or maternal-fetal death. etiopathogenisis is not clear up to now.For the past few years, immunology becomes hot spot.Costimulatory molecules play a important role in immunity balance, the most important molecule of all is B7 :leucocyte differentiation antigen (CD28)/ cytotoxicity T lymphocyte(CTLA-4).Costimulation molecules especially B7:CD28/CTLA-4 as a requisition not only influence T lymphocyte activation and proliferation but also is important regulatory factor of T cell activation .Researching costimulation molecules deeply is to deepen the recognition preeclampsia immunologic mechanism, Accordingly providing clinical immunotherapy prove.Objective :1 Now the etiopathogenisis of Hypertensive disorders complicating pregnancy still is not clear. for the past few years, immunology becomes to study hot spot . the ratio of Th1/ Th2 unbalance has obtained confirm.but the cause of Th1/ Th2 unbalance is not clear.Therefore,the study is to research the cause of Th1/ Th2 unbalance and provid new ideas for treatment and prevention of preeclampsia by determining expression and effectiveness of cluster of differentiation 28 and cytotoxic T lymphocyte antigen 4 in maternal blood and uterus decidua lymphocyte in pregnancy advanced stage(>28 week).2 To explore in the role of expression of CD28 and CTLA-4 costimulative molecules on peripheral blood and decidual lymphocytes of early-onset preeclampsia and delayed preeclampsia in maternal-fetal immune regulation.Methods :1 The study subject;1.1The study group (the preeclampsia group): 24 patients who had prenatal examinations and delivered in the Obstetrics of the Second Hospital of HeBei Medical University were selected from December 2006 to April 2007.They were divided into two groups: early-onset preeclampsia (<34week)and delayed preeclampsia(>34week). 12 cases early-onset preeclampsia patients who mean ages are 27.83 years,mean gestational weeks are 31.86 weeks;and 12 cases delayed preeclampsia patients who mean ages are 27.44 years ,mean gestational weeks are 37.86 weeks. It applies flow cytometry to detect expression of CD28 and CTLA-4 of peripheral and decidual lymphocytes in CD3+CD4+T and CD3+CD8+T cell. 1.2 The control group :10 healthy third trimester pregnant women were selected to serve as the control group. mean ages of them are 26.87 years,mean gestational weeks of them are 38.6weeks.It apply flow cytometry to detect expression of CD28 and CTLA-4 of peripheral and decidual lymphocytes in CD3+CD4+T and CD3+CD8+T cell .1.3 Diagnosis criteria of preeclampsia were as follows: after 20 weeks of gestation , blood pressure≥140/100mmHg; proteinuria≥0.3g/24 hours or proteinuria masccline; have or not swollen ;serum creatinine>106umol/L; platelet count<100×109/L; microangiothic hemolysis ( elevation of serum LDH ) ; elevation of serum ALT or AST; persistent headache or other disturbances of cranial nerve or vision ; persistent discomfort of the epigastrium. gestational weeks early-onset preeclampsia were 34weeks ago, gestational weeks delayed preeclampsia were after 34weeks.Ages were no significant difference among early-onset preeclampsia , delayed preclampsia and healthy control(p>0.05). gestational weeks were significant difference in the early-onset preeclampsia compare to delayed preclampsia and healthy control(p<0.05),but the levels of CD28 and CTLA-4 were no significant difference in the early-onset preeclampsia compare to delayed preclampsia,therefore, gestational weeks can not influence the levels of CD28 and CTLA-4.2 Sample collecting: blood preparation collecting:3 groups preganancy wemen were drawn-off antebrachium ulnar vein blood 1ml( pretherapy hemospasia),which all were infused heparin asepsis tube to deal with.deciduas tissue sample collecting: after placental expulsion,get uterus deciduas tissue 4G to deal with.3 The experiment method:Use flow cytometry method to determine the levels of CD28 and CTLA-4 in peripheral and decidual lymphocytes.Results :1 The expression of CD3+ T cell were no significant difference on peripheral among early-onset preeclampsia,delayed preclampsia and healthy control.The expression of CD4+ T cell increased on peripheral in the early-onset and delayed preeclampsia compared to healthy control, they were statistically significant(P<0.05). The expression of CD4+ T cell were no significant difference on peripheral in the delayed preeclampsia compared to early-onset preeclampsia(P>0.05). The expression of CD8+ T cell significantly decreased on peripheral in the early-onset and delayed preeclampsia compared to healthy control(p<0.05). The expression of CD8+ T cell were no significant difference (P>0.05)on peripheral in the delayed preeclampsia compared to early-onset preeclampsia.2 The ratio of CD4+ /CD8+ T cell increased on peripheral in the early-onset and delayed preeclampsia compared to healthy control, they were statistically significant(P<0.05).3 The expression of CD28 on CD3+CD4+ T and CD3+CD8+ T cell on peripheral in preeclampsia patients were no difference than those in healthy control(p>0.05); so were the early-onset preeclampsia and delayed preeclampsia.The expression of CTLA-4 on CD3+CD4+ T and CD3+CD8+ T T cell on peripheral in preeclampsia patients significantly increased than those in healthy control(p<0.05);The expression of CTLA-4 in delayed preeclampsia patients decreased than early-onset preeclampsia.,but they were not statistically significant(p>0.05).4 The ratio of CTLA-4/CD28 on CD3+T lymphocyte increased significantly on peripheral in the preeclampsia compared to healthy control, they were statistically significant(P<0.05).5 The expression of CD28,CTLA-4 on the deciduas were different from peripheral's, the expression of CD28,CTLA-4 on the deciduas were significantly lower than peripheral's.6 CD3+CD28+ and CD3+CTLA-4+ were no correlations.Conclusion :1 The high exspession of CTLA-4 promote CD4+T cell over- activation to Th1 differentiation,inducing the ratio of Th1/ Th2 unbalance , which might lead to preeclampsia,Therefor,the man-made interdiction of CTLA-4 may control the occurrence and progress of preeclampsia,which may be a new immunity assistant method to treat preeclampsia.2 Abnormal expressions of CD4/CD8 on T lymphocytes Subpopulations lead to the imbalanced maternal-fetal immune function in the patients with preeclampsia.3 The exspession of CD28 and CTLA-4 in the T lymphocyte on the deciduas were different from peripheral's.The exspession of CD28 and CTLA-4 in the T lymphocyte on the deciduas were lower than peripheral's,because the context of T lymphocyte on the deciduas were low.4 The expression of T lymphocyte subpopulations CD28 and CTLA-4 is no difference in the early-onset preeclampsia in comparison to delayed preeclampsia, The exspession of CTLA-4 were not correlation with preeclampsia morbidity time successively.5 CD28 is not correlation with CTLA-4 in the peripheral of preeclampsia patients,it explains that CD3+CD28+ were no change when the expression of CD3+CTLA-4+ increased in the preeclampsia group.