| Background:End stage renal disease(ESRD)patients also present immune activation and immune deficiency status marked by systemic inflammatory response syndrome,and the incidence rate and mortality of infections increase significantly.Further study on the mechanism of immune dysfunction in ESRD and the establishment of effective treatment interventions are of great significance to improve the prognosis of ESRD.NK cell activating receptor NKG2D(natural killer group 2,numberd)is widely expressed in natural killer(NK)cells,CD8+T cells,CD4+T cell subsets,NKT cells(iNKT)and NK cells γδ T cell surface is the key receptor for activating immune effector cells in infection,tumor and autoimmune diseases.Its number and activity can reflect the function of NK cells.MICA is a NKG2D specific ligand,which is mainly expressed in normal gastrointestinal epithelial cells.When the target cells are infected or gene mutation occurs,its expression level is significantly up-regulated.After being recognized and bound by NKG2D,the activation receptor on the surface of NK cells,MICA activates the killing effect of NK cells on the target cells.Tumor immune research found that the excessive expression of MICA on the surface of tumor cells and the formation of soluble MICA(sMICA)after shedding into the blood can specifically bind to NKG2D,down regulate the expression of NKG2D on the surface of NK cells,greatly reduce the activity of NK cells,so that tumor cells can escape the immune surveillance of NK cells.the mechanism of NKG2D and its soluble ligand sMICA in tumor immunity has been a lot of research,but the expression and its mechanism in ESRD immunodeficiency are still unclear.Objective:Objective to investigate the expression of NK cell activating receptor NKG2D and its soluble ligand SMICA in peripheral blood of ESRD dialysis patients,and its mechanism and clinical significance in ESRD immune disorder.Methods:1.The subjects were divided into 50 patients group and 20 control group.The percentages of NKG2D positive CD3,CD56 and CD27 cells in PBMCs were detected by flow cytometry;The relative expression of NKG2D mRNA in PBMCs was detected by real-time PCR;The content of sMICA protein in peripheral blood was detected by ELISA.The differences between the experimental data groups and the correlation among the three experimental indexes were analyzed.The significant difference between the groups and other clinical indicators were analyzed.2.The percentage content of NKG2D on the surface of peripheral blood mononuclear cells,the relative expression of NKG2D mRNA,and the content of sMICA protein in peripheral blood of patients with peritoneal dialysis(PD)and hemodialysis(HD)were compared.3.ELISA method was used to detect the sMICA protein content in peripheral blood of 10 volunteers before and after dialysis.4.All data were manually input into Excel spreadsheet for processing and analyzed by Stata se12.0 software.The measurement data of normal distribution are expressed as mean±standard deviation,and the measurement data of non normal distribution are expressed as median(range).The two groups of data conform to the normal distribution,and the independent sample t test is used.The analysis of variance is used between the three groups.The Pearson correlation analysis is used to analyze the correlation between the two groups of data,and the Spearman correlation analysis is used to analyze the correlation between the two groups of data.All analyses were statistically significant(P<0.05).Result:1.The percentage of NKG2D+CD56+cells in ESRD group(80.742%±98%)was significantly lower than that in NC group(96.32%±1.28%),P=0.0075.It was negatively correlated with the course of ESRD(r=-0.4611,P<0.001)and the peripheral blood monocyte count(r=-0.44,P=0.0405).2.There was no significant difference in the relative expression of NKG2D mRNA between ESRD group and NC group.3.The sMICA protein content in ESRD Group[228.3(52.01,356.5)]was higher than that in NC Group[110.4(6.98,227.9)],P<0.0001.It was positively correlated with the course of disease(r=0.3957,P=0.045),positively correlated with the peripheral blood monocyte count(r=0.4593,P=0.0191),and negatively correlated with the percentage of NKG2D+CD56+cells in peripheral blood(r=-0.692,P<0.001).4.The percentage of NKG2D+CD56+cells in peritoneal dialysis group was higher than that in hemodialysis group(P=0.0238)5.There was no significant difference in SMICA protein content in peripheral blood of ESRD patients before and after hemodialysis.Conclusion:1.The decreased expression of NKG2D on peripheral blood NK cells in ESRD dialysis patients is an important reason that ESRD patients are prone to infection.2.The content of sMICA protein in peripheral blood of ESRD dialysis patients is higher than the normal level.Excessive sMICA specific binding with NKG2D receptor can lead to the down-regulation of NKG2D expression on the surface of NK cells.3.The expression level of NKG2D on the surface of NK cell membrane in ESRD peritoneal dialysis patients was higher than that in hemodialysis patients.4.Hemodialysis can not effectively control the down-regulation of NKG2D expression by high level of sMICA in ESRD patients.Figure[12]Table[12]Reference[37]... |
PDF Full Text Request