程序性死亡因子-1在腹腔感染致脓毒症患者外周血T细胞及中性粒细胞的表达

Expression of programmed death-1 in peripheral blood T cells and neutrophils in patients with sepsis caused by intra-abdominal infection

目的探讨腹腔感染(IAI)致脓毒症患者程序性死亡因子-1(PD-1)在外周血CD4^+、CD8^+T细胞和中性粒粒细胞上的表达。方法收集2016年2月至2017年9月本院普外科及重症监护病房收治的32例IAI致脓毒症患者,根据确定脓毒症与感染性休克的流程分为脓毒症组(n=17)和感染性休克组(n=15),另随机选20例健康者作为对照组。所有研究对象入组时行序贯器官衰竭评估(SOFA)评分,24 h行急性生理和慢性健康评分-Ⅱ(APACHE-Ⅱ)。3组研究对象入组时抽取外周血,采用流式细胞仪器及FlowJoV10软件分析PD-1、程序性死亡因子配体1(PD-L1)在健康对照组、脓毒症组、感染性休克组外周血CD4^+、CD8^+T细胞和中性粒细胞上的表达情况,采用Pearson相关分析感染性休克组CD4^+T细胞PD-1的表达与APACHE-Ⅱ、SOFA的相关性。结果与健康对照组比较,脓毒症组、感染性休克组患者外周血CD4^+、CD8^+T细胞上PD-1表达增加,感染性休克组表达更高(均P<0.05);与健康对照组比,脓毒症组、感染性休克组患者外周血CD4^+、CD8^+T细胞上PD-L1虽均表达增加,但差异均无统计学意义(均P>0.05);与健康对照组比较,脓毒症组、感染性休克组患者外周血中性粒细胞上PD-1、PD-L1均表达增加,感染性休克组患者表达更高,差异均有统计学意义(均P<0.05);与脓毒症组比,感染性休克组患者APACHE-Ⅱ和SOFA评分均增高,差异有统计学意义(均P<0.05),感染性休克组患者CD4^+T细胞PD-1表达与APACHE-Ⅱ和SOFA评分成正相关(r=0.850,P=0.000;r=0.0.901,P=0.000)。结论PD-1在IAI致脓毒症患者外周血T细胞及中性粒细胞的表达增加,且与SOFA评分、APACHE-Ⅱ呈相关性,可能可用于评估病情的严重程度并作为IAI脓毒症治疗的新靶点。

Objective To investigate the expression of programmed death-1(PD-1)in peripheral blood CD4^+,CD8^+T cells and neutrophils in patients with sepsis caused by intra-abdominal infection(IAI).Methods A total of 32 patients with sepsis caused by IAI admitted to ICU or Department of General Surgery,Lianyungang Hospital Affiliated to Xuzhou Medical University between February 2016 and September 2017 were enrolled in the study.According to the procedure for determining sepsis and septic shock,they were divided into sepsis group(n=17)and septic shock group(n=15).A cohort of 20 healthy subjects were recruited as the control group.All the subjects underwent sequential organ failure assessment(SOFA)at enrollment,and the Acute Physiology and Chronic Health Evaluation-Ⅱ(APACHE-Ⅱ)at 24 hours after enrollment.Peripheral blood was collected from the three groups at enrollment.The expression of PD-1 and programmed death ligand 1(PD-L1)of peripheral blood CD4^+T,CD8^+T cells and neutrophils in the sepsis group,septic shock group and control group were analyzed by flow cytometry and FlowJo_V10 software.The correlations between PD-1 expression of CD4^+T cells in the septic shock group and APACHE-Ⅱand SOFA were studied by Pearson correlation analysis.Results Compared with the control group,the expression level of PD-1 was increased in peripheral blood CD4^+and CD8^+T cells in the sepsis group and the septic shock group,and was higher in the septic shock group than that in the sepsis group(both P<0.05).Compared with the control group,the expression level of PD-L1 in peripheral blood CD4^+and CD8^+T cells in the sepsis group and the septic shock group was increased,but the differences were not statistically significant(P>0.05).Compared with the control group,the expression levels of PD-1 and PD-L1 in peripheral blood neutrophils were increased in the sepsis group and the septic shock group,and were higher in the septic shock group than those in the sepsis group with statistically significant differences(all P<0.05).Compared with the sepsis group,the APACHE-Ⅱand SOFA scores in the septic shock group were increased,with statistically significant differences(both P<0.05).The PD-1 expression level in CD4^+T cells of septic shock group was positively correlated with APACHE-Ⅱand SOFA scores(r=0.850,P=0.000;r=0.901,P=0.000,respectively).Conclusion PD-1 expression levels in peripheral blood T cells and neutrophils are increased in patients with sepsis caused by IAI,and are correlated with SOFA and APACHE-Ⅱscores,and therefore are useful for severity assessment of the disease and as a new target for the treatment of sepsis caused by IAI.