干扰素疗效与慢性乙型肝炎患者外周血CD8^+T细胞程序性死亡受体-1和T细胞免疫球蛋白黏蛋白分子3表达的关系  

Relationship between interferon-alpha efficacy and the expression of programmed death 1 and T-cell immunoglobulin and mucin domain-containing molecule 3 on peripheral blood CD8^+ T cells in patients with chronic hepatitis B

作　　者：王海燕[1] 王银铃 朱莉[1] 陈慧[1] 钱峰[1] 李明[1] 朱伟[1] 张雪华[1] 胥萍[1] 朱传武[1] Wang Haiyan, Wang Yinling, Zhu Li, Chen Hui, Qian Feng, Li Ming, Zhu Wei, Zhang Xuehua, Xu Ping, Zhu Chuanwu(Department of Hepatology, The Fifth People＇s Hospital of Suzhou, Suzhou 215007, Chin)

机构地区：[1]苏州市第五人民医院肝病科,苏州市215007

出　　处：《中华实验和临床感染病杂志（电子版）》2018年第1期40-45,共6页Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)

基　　金：苏州市科技局和苏州市卫生局兴卫基金项目(No.KJXW2011031);苏州市感染性疾病临床医学中心项目(No.SZZX201508);苏州市临床重点病种诊疗项目(No.LCZX201315);江苏省卫生计生委面上项目(No.2017068)

摘　　要：目的探讨干扰素抗病毒疗效与慢性乙型肝炎(CHB)患者外周血CD8^+T细胞程序性死亡受体1(PD-1)和T细胞免疫球蛋白黏蛋白分子3(Tim3)表达的关系。方法以72例HBe Ag阳性CHB患者作为研究对象,分别采集干扰素治疗前和治疗12个月的抗凝外周静脉血,同期以30例健康人作为研究对照,用流式细胞技术检测CD8^+T细胞PD-1和Tim3的表达。结果干扰素治疗前,CHB患者外周血CD8^+T细胞PD-1和Tim3表达的中位百分率分别为35.5%和4.8%,均显著高于健康对照组(29.3%和3.6%),差异均具有统计学意义(U=805.0、P=0.043,U=741.5、P=0.013)。干扰素治疗12个月时,患者CD8^+T细胞PD-1和Tim3的表达分别为32.7%和4.1%,较治疗前显著下降,差异具有统计学意义(Z=3.305、P=0.001,Z=2.065、P=0.039);在获得HBe Ag血清学转换者中,CD8^+T细胞PD-1和Tim3表达的中位百分率均显著低于无转换者,差异均具有统计学意义(U=209.0、P<0.001,U=302.0,P<0.001);在ALT复常与异常者之间,两项指标的中位百分率差异无统计学意义(U=229.5、P=0.635,U=209.5、P=0.405);在HBV DNA载量低于检测下限者中,CD8^+T细胞PD-1表达的中位百分率显著低于病毒仍可检测的患者(U=371.5、P=0.011),而CD8^+T细胞Tim3的表达两者差异无统计学意义(U=558.0、P=0.727)。结论 CHB患者外周血CD8^+T细胞PD-1和Tim3呈高表达状态,干扰素治疗可以下调其表达,并且其表达降低与干扰素疗效有关。Objective To investigate the association of interferon-alpha （IFN-α） antiviral efficacy and the expression of programmed death 1 （PD-1） and T-cell immunoglobulin and mucin domain-containing molecule 3 （Tim3） on peripheral blood CD8＋T cells in patients with chronic hepatitis B （CHB）. Methods Total of 72 CHB patients with HBeAg positive were collected, and their anti-coagulation peripheral venous blood were collected from each patient at the beginning and the end of 12 months of IFN-α therapy. Thirty cases of healthy individuals were enrolled as controls. PD-1 and Tim3 on CD8＋T cells were detected by flow cytometry. Results Before IFN-α treatment, the median percentage of PD-1 and Tim3 on peripheral blood CD8＋T cells was 35.5% and 4.8% in CHB, respectively, and both were higher than the corresponding index in healthy control group （29.3% and 3.6%）, with significant differences （U = 805.0, P = 0.043; U = 741.5, P = 0.013）. At the end of 12 months of IFN-α therapy, the median percentage of PD-1 and Tim3 on CD8＋T cells was 32.7% and 4.1% in CHB patients, respectively, and significantly decreased than those before treatment （Z = 3.305, P = 0.001; Z = 2.065, P = 0.039）. The median percentage of the two molecule expression was significantly lower in patients who achieved HBeAg seroconversion than those of patients without HBeAg seroconversion, with significant differences （U = 209.0, P 〈 0.001; U = 302.0, P〈0.001）.The two median percentages were without significant difference between ALT normalization and abnormalization groups （U = 229.5, P = 0.635; U = 209.5, P = 0.405）. The median percentage of PD-1 on CD8＋T cells was significantly lower in patients with HBV DNA undetectable than those with detectable HBV DNA （U =371.5, P = 0.011）, which was not significantly different between the two groups of patients （U = 558.0, P = 0.727）. Conclusions A higher expression of PD-1 and Tim3 on peripheral blood CD8＋T cells was presented in CHB patients, which could be dow

关 键 词：肝炎 乙型 慢性 干扰素 外周血CD8+T淋巴细胞 程序性死亡受体-1 T细胞免疫球蛋白黏蛋白分子3 

分 类 号：R512.62[医药卫生—内科学]