Expression Of PD-1?LAG-3 And Its Ligand In Peripheral Blood And Decidua Of Patients With Severe Early-onset Preeclampsia

Research background:Preeclampsia(PE)is a severe gestational hypertension with an incidence of up to 10%.Characterized by hypertension and proteinuria,this disease,which usually occurs after 20 weeks of gestation,can injure many systems.Severe early-onset preeclampsia is a subtype of PE which refers to the cases that occur before 34 weeks of pregnancy.Currently,the specific pathogenesis of preeclampsia is still unclear.In recent years,the role of maternal immune system overactivation in the pathogenesis of preeclampsia has gradually attracted the attention of relevant researchers.Programmed cell death 1 and its ligand(PD-1/PD-L1)are one of the most deeply studied immune checkpoints.Early experiments showed that by binding with its ligand PD-L1 or PD-L2.PD-1 could produce negative costimulatory effect on T cells,and resulted in down-regulating of T cells activation.As a co-inhibitory molecule of PD-1,the high expression of the lymphocyte activation gene-3(LAG-3)is closely related to the pathogenesis of a variety of autoimmune diseases,infectious diseases and tumors.Studies have confirmed that LAG-3 had played an important role in tumor immune escape.Purpose and Intend:By studying the expression change of PD-1,LAG-3 and its ligand in peripheral blood and decidua of severe early-onset preeclampsia patients,we explored the correlativity between PD-1/PD-L1,LAG-3 and the pathogenesis of preeclampsia,analyzed the role it may play in the onset of preeclampsia and its clinical significance,subsequently proposed new ideas for the research on the pathogenesis of preeclampsia and provided important theoretical basis,and finally achieved the propose of presenting new directions and targets for clinical diagnosis and treatment.MethodsA total of 27 patients with severe early-onset preeclampsia who visited Shandong provincial Hospital and gave birth between May 2019 and January 2020 were selected as the experimental group,while 13 normal pregnant women who visited Shandong provincial Hospital and gave birth during the same period were selected as the control group.Their peripheral blood and decidual tissues were collected.Using flow cytometry analysis technology,we detected the expression level of LAG-3,PD-1 and PD-L1 on T cells.Regulatory T cells(T-reg cells),natural killer cells(NK cells),NKT cells and innate lymphoid cells(ILCs).Through comparison the expression differences between the experimental group and control group,we analyzed the correlation of PD-1,PD-L1,LAG-3 and preeclampsia.Result1.In peripheral blood of severe early-onset preeclampsia patients,the expression of PD-1 on CD3+T cells and CD8+T cells was significantly down-regulated.On CD3+T cells,the positive rate of PD-1 in the experimental group was 15.74±1.356,while that in the control group was 22.62±2.181(P<0.01).On CD8+T cells,the positive rate of PD-1 in the experimental group was 12.36±1.326,and that in the control group was 22.37±2.814(P<0.001).The changes on CD4+T cells were not statistically significant(P>0.05);2.In the decidual tissues,the expression of PD-1 on T cells was down-regulated.The positive rate of PD-1 was 35.68±3.485 in the experimental group and 48.70±5.100 in the control group(P<0.05).There was no significant change in the expression of PD-1 on NK cells and NKT cells(P>0.05);3.The expression of PD-L1 and LAG-3 in peripheral blood mononuclear cells was extremely low and could not be detected.There was no significant difference in the expression of PD-L1 and LAG-3 on decidual T cells,NK cells and NKT cells(P>0.05);4.In peripheral blood,PD-1 expression on CD3+T cells was positively correlated with gestational week of termination and neonatal birth weight(P<0.05),while it was negatively correlated with urinary protein and LDH levels in patients(P<0.05).The expression of PD-1 on CD8+T cells was positively correlated with gestational week of termination and neonatal birth weight(P<0.05),and negatively correlated with the levels of urine protein,uric acid.LDH and BNP(P<0.05).5.On T cells of decidual tissues,there was no significant correlation between the expression of PD-1 and the gestational week of termination or the birth weight of the newborn(P>0.05),but it was negatively correlated with the levels of uric acid,LDH and BNP in the patients(P<0.05).ConclusionThe PD-1/PD-L1 pathway may play an important role in the pathogenesis of preeclampsia by regulating the activity and killing ability of T cells and regulating the immune tolerance between maternal and the fetus.The expression level of PD-1 may be negatively correlated with the severity of clinical symptoms and signs of PE patients.The role of LAG-3 in this process is undefined.