HBV相关性肝病患者外周血PBMCs表面Tim-3、PD-1表达水平检测及意义

Detection and significance of Tim-3 and PD-1 expression levels on the surface of PBMCs in peripheral blood of patients with HBV-related liver diseases

目的分析乙型肝炎病毒(HBV)感染后相关肝病患者外周血单个核细胞(PBMCs)表面T细胞免疫球蛋白黏蛋白分子-3(Tim-3)、程序性死亡受体-1(PD-1)表达水平变化及意义。方法选取2017年1~12月川北医学院附属医院HBV携带者20例,慢性乙型肝炎(CHB)患者30例,重型乙型肝炎患者20例,乙肝肝硬化患者30例,肝细胞癌患者20例,以同期20例健康体检者作为健康对照组。检测各研究对象外周血PBMCs表面Tim-3、PD-1表达水平。结果 PBMCs表面Tim-3、PD-1表达水平在健康对照组最低,与HBV携带组比较差异无统计学意义(P>0.05),随着病情加重,PBMCs表面Tim-3、PD-1表达水平逐渐升高,在重型乙型肝炎组、肝细胞癌组最高,各组患者PBMCs表面Tim-3、PD-1表达水平与健康对照组、HBV携带者组比较,差异有统计学意义(P<0.05);HBV感染患者PBMCs表面Tim-3、PD-1表达水平与HBV DNA载量呈负相关(r=-0.431和-0.422,均P<0.05),与ALT、AST水平呈正相关(r=0.214、0.325、0.234和0.354,均P <0.05);HBV感染患者总体PBMCs表面Tim-3的表达水平与PD-1表达量呈正相关(r=0.967,P <0.05)。结论免疫负性调节因子Tim-3、PD-1与HBV相关性肝病患者肝组织炎症及纤维化发生相关,对Tim-3、PD-1水平调节可能为其临床免疫治疗提供新思路。

Objective To analyze change and meaning of T cell immune globulin sticky protein molecules-3(T cell immunoglobulin mucin molecule-3,Tim-3)and procedural death receptor-1(programmed cell death protein-1,PD-1)on the surface of peripheral blood mononuclear cells(Human peripheral blood mononuclear cells,PBMCs)in patients with hepatitis B virus(hepatitis B virus,HBV)related liver disease.Methods From January 2017 to December 2017,20 hepatitis B virus carriers,30 chronic hepatitis B patients,20 severe hepatitis B patients,30 hepatitis B cirrhosis patients and 20 hepatitis B liver cancer patients were compared with 20 healthy subjects selected as the healthy control group,and the levels of Tim-3 and PD-1 on the surface of PBMCs in the peripheral blood of all subjects were tested.Results Levels of Tim-3 and PD-1 on PBMCs surface were the lowest in healthy control group, compared with those in hepatitis B virus carriers group, and the difference had no statistical significance(P > 0.05). As the aggravating of illness, the levels of Tim - 3 and PD-1 on PBMCs surface increased, which wasthe highest in severe hepatitis B group and hepatitis B liver cancer group. The difference among the levels of Tim-3 and PD-1 on PBMCs surface in other groups were statistically significant, compared with those in healthy groupand hepatitis B virus carrier group (P < 0.05);the expression levels of Tim-3 and PD-1 on the PBMCs surface ofpatients with HBV infection were negatively correlated with the DNA load of HBV (r = -0.431, -0.422, P < 0.05),and positively correlated with ALT and AST levels (r = 0.214, 0.325, 0.234 and 0.354, P < 0.05);there was asignificant positive correlation between the expression level of Tim-3 and PD-1on the PBMCs surface of HBVinfection patients (r = 0.967, P < 0.05). Conclusions The negative immune regulatory factors Tim-3 and PD-1 arekey factors for the occurrence of liver inflammation and fibrosis in HBV-related liver diseases, and the regulationof Tim-3 and PD-1 level may provide a new idea for clinical immunotherapy.