Clinical Study On Monitoring PD-1 Expression Rate Of T Cells In Patients With Sepsis

Objective: This study intends to observe the dynamic change pattern of PD-1 expression rate of peripheral blood T cells in sepsis patients and analyze the correlation between the change characteristics of T cell PD-1 expression rate and the concentration,severity and28-day prognosis of inflammatory mediators.Methods: The method used in this study was an observational,prospective,single-center study,and sepsis patients treated in the ICU of the Fifth Affiliated(Zhuhai)Hospital of Zunyi Medical University from January 2020 to December 2020,along with healthy volunteers,were used as subjects.Peripheral venous blood specimens were collected at days 1,3 and 7 after enrollment.Meanwhile,we performed flow cytometric analysis to measure T cell subsets(ratios of CD4+ and CD8+ T cells),T cell PD-1 expression,and CD4+/CD8+ ratio.In addition,IL-6,IL-10,and TNF-α levels were measured by ELISA.The levels of CRP and PCT were measured by immunochemiluminescence assay.To analyze and compare the differences between the expression rates of inflammatory mediators,T cell subsets and T cell PD-1 at different time points in each group of subjects;to compare the expression rates of T cell PD-1 and inflammatory mediators in peripheral blood of sepsis patients at each time point,with the help of Pearson correlation analysis.APACHE Ⅱ score,T-cell subpopulation ratio,and SOFA score.Factors to independently predict the risk of 28-day mortality among septic cases were analyzed by logistic regression,and diagnostic fold was determined according to ROC.Results: The subjects of this study were 164 septic patients and 51 healthy individuals(controls).Of them,those 164 cases were divided as sepsis(n=91)or septic shock(n=73)group,depending on the occurrence of shock.As a result,septic shock group had markedly increased APACHE Ⅱ score in comparison with sepsis group,along with markedly increased SOFA score at each time point(P<0.001).IL-6,IL-10,and TNF-α expression remarkably increased in septic shock and sepsis groups in comparison with control group at each time point,and were also significantly higher in the septic shock group compared to the sepsis group(P<0.001).The T-cell subsets CD4+ ratio,CD8+ ratio,and CD4+/CD8+at the three time points in septic shock group and sepsis group decreased in comparison with control group,and those in septic shock group remarkably decreased in comparison with sepsis group(P<0.001).In terms of T-cell PD-1 expression at the three time points,septic shock and sepsis groups had increased levels in comparison with control group,and the septic shock group showed a higher expression compared to the sepsis group(P<0.001).For septic cases,PD-1 levels in T cells were in direct proportion to APACHE Ⅱ score,SOFA score and inflammatory mediators(P<0.001)and negatively correlated with T cell subsets(P<0.001).Upon logistic regression analysis,CD4+ T-cell PD-1 versus APACHE Ⅱscore on the first day after enrollment(P<0.001)were identified as the factors to independently predict the 28-day mortality among septic cases.ROC curve results showed that CD4+ T-cell PD-1 expression on day 1 after enrollment predicted the area under the28-day mortality curve in sepsis patients to be 0.893,with a best predicted value of21.93%(P<0.001).Conclusion: Peripheral blood T-cell PD-1 overexpression can occur in patients with sepsis and septic shock,and its elevated levels correlate with APACHE Ⅱ score,SOFA score,T-cell subsets,and inflammatory mediator concentration levels.APACHE Ⅱ score and PD-1 level in CD4+ T cells on day 1 post-enrollment are identified as the factors to independently predict the risk of 28-day mortality among septic cases.PD-1 expression rate monitoring will provide new ideas for immune monitoring in sepsis and provide a clinical basis for immune modulation in sepsis.