切换至 "中华医学电子期刊资源库"

中华实验和临床感染病杂志(电子版) ›› 2018, Vol. 12 ›› Issue (01) : 40 -45. doi: 10.3877/cma.j.issn.1674-1358.2018.01.008

所属专题: 文献

临床论著

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
王海燕1, 王银铃1, 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   
  1. 1. 215007 苏州市,苏州市第五人民医院肝病科
  • 收稿日期:2017-03-20 出版日期:2018-02-15
  • 通信作者: 朱传武
  • 基金资助:
    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)

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

Haiyan Wang1, Yinling Wang1, Li Zhu1, Hui Chen1, Feng Qian1, Ming Li1, Wei Zhu1, Xuehua Zhang1, Ping Xu1, Chuanwu Zhu,1   

  1. 1. Department of Hepatology, The Fifth People’s Hospital of Suzhou, Suzhou 215007, China
  • Received:2017-03-20 Published:2018-02-15
  • Corresponding author: Chuanwu Zhu
  • About author:
    Corresponding author: Zhu Chuanwu, Email:
引用本文:

王海燕, 王银铃, 朱莉, 陈慧, 钱峰, 李明, 朱伟, 张雪华, 胥萍, 朱传武. 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[J/OL]. 中华实验和临床感染病杂志(电子版), 2018, 12(01): 40-45.

Haiyan Wang, Yinling Wang, Li Zhu, Hui Chen, Feng Qian, Ming Li, Wei Zhu, Xuehua Zhang, Ping Xu, Chuanwu Zhu. 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[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2018, 12(01): 40-45.

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HBeAg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HBeAg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 downregulated by IFN-α therapy, and the decreased expression was associated with the efficacy of IFN-α treatment.

表1 CHB患者和对照组的临床基线资料
表2 CHB患者与对照组外周血CD8+ T细胞PD-1和Tim3的表达
表3 干扰素治疗前后CHB患者外周血CD8+ T细胞PD-1和Tim3的表达
图1 CHB患者干扰素治疗不同应答患者外周血CD8+ T细胞PD-1和Tim3的表达
图2 HBeAg血清学转换组与健康对照组外周血CD8+ T细胞PD-1和Tim3的表达
[1]
Xu P, Chen YJ, Chen H, et al. The expression of programmed death-1 in circulating CD4+and CD8+T cells during hepatitis B virus infection progression and its correlation with clinical baseline characteristics[J]. Gut Liver,2014,8(2):186-195.
[2]
Wu W, Shi Y, Li J, et al. Tim3 expression peripheral T cell subsets correlates with disease progression in hepatitis B infection[J]. Virol J,2011,8:113.
[3]
Jin HT, Anderson AC, Tan WG, et al. Cooperation of Tim3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection[J]. Proc Natl Acad Sci USA,2010,107(33):14733-14738.
[4]
Li Z, Li N, Zhu Q, et al.Genetic variations of PD1 and TIM3 are differentially and interactively associated with the development of cirrhosis and HCC in patients with chronic HBV infection[J]. Infect Genet Evol,2013,14:240-246.
[5]
中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2010年版)[J].中华内科杂志,2011,50(2):168-179.
[6]
Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death[J]. EMBO J,1992,11(11):3887-3895.
[7]
Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance[J].Trends Immunol,2006,27(4):195-201.
[8]
Carolina B, Paola F, Caterina V, et al.Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection[J]. J Virol,2007,81(8):4215-4225.
[9]
Peng G, Li S, Wu W, et al. PD-1 upregulation is associated with HBVspecific T cell dysfunction in chronic hepatitis B patients[J]. Mol Immunol,2008,45(4):963-970.
[10]
Selenko-Gebauer N, Majdic O, Szekeres A, et al. B7-H1 (programmed death-1 ligand) on dendritic cells is involved in the induction and maintenance of T cell anergy[J]. J Immunol,2003,170(7):3637-3644.
[11]
Evans A, Riva A, Cooksley H, et al. Programmed death 1 expression during antiviral treatment of chronic hepatitis B: impact of hepatitis B e-antigen seroconversion[J]. Hepatology,2008,48(3):759-769.
[12]
Feng X, Feng J. Clinical significance of Tim3-positive T cell subsets in patients with multiple sclerosis[J]. J Clin Neurosci,2016,34:193-197.
[13]
陈旭丹,刘琼,李新华,等.慢性HBV感染者HBV特异性CD8+T细胞Tim-3和PD-1的表达水平及其与IFN-γ产生的相关性研究[J/CD].中华实验和临床感染病杂志(电子版),2013,7(5):665-669.
[14]
Oomizu S, Arikawa T, Niki T, et al. Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner[J]. Clin Immunol,2012,143(1):51-58.
[15]
Sada-Ovalle I, Chávez-Galán L, Torre-Bouscoulet L, et al. The Tim3-galectin 9 pathway induces antibacterial activity in human macrophagesinfected with Mycobacterium tuberculosis[J]. J Immunol,2012,189(12):5896-5902.
[16]
Sakuishi K, Jayaraman P, Behar SM, et al. Emerging Tim-3 functions in antimicrobial and tumor immunity[J]. Trends Immunol,2011,32(8):345-349.
[17]
Kang CW, Dutta A, Chang LY, et al.Apoptosis of tumor infiltrating effector TIM-3+CD8+T cells in colon cancer[J]. Sci Rep,2015,5:15659.
[18]
Zhu C, Anderson AC, Kuchroo VK. TIM-3 and its regulatory role in immune responses[J]. Curr Top Microbiol Immunol,2011,350(2):1-15.
[19]
Ma L, Cai YJ, Yu L, et al.Treatment with telbivudine positively regulates antiviral immune profiles in Chinese patients with chronic hepatitis B[J].Antimicrob Agents Chemother,2013,57(3):1304-1311.
[20]
王琳,赵春楠,祁松楠,等.慢性乙型肝炎患者外周血T淋巴细胞表面共刺激分子表达量变化及其意义[J].中华检验医学杂志,2014,37(2):105-109.
[21]
Wang L, Zhao C, Peng Q, et al. Expression levels of CD28, CTLA-4, PD-1 and Tim-3 as novel indicators of T-cell immune function in patients with chronic hepatitis B virus infection[J]. Biomed Rep,2014,2(2):270-274.
[22]
Ma H, Zhang HH, Wei L. Frequency of T-cell FoxP3+Treg and CD4+/CD8+PD-1 expression is related to HBeAg seroconversion in hepatitis B patients on pegylated interferon[J]. Chin Med J,2013,126(2):267-273.
[1] 李璐璐, 马利红, 金佳佳, 谷伟. 干扰素基因刺激因子通过肺巨噬细胞胞葬功能调控急性肺损伤小鼠修复的研究[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(02): 97-103.
[2] 郑宝英, 黄小兰, 贾楠, 朱春梅. 儿童难治性肺炎支原体肺炎早期预警指标[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(04): 215-221.
[3] 李亚萍, 张萌, 李博驹, 刘晨瑞, 苟国娥, 李嘉昕, 张玉凤, 席淼, 邓慧玲. 干扰素诱导蛋白16-干扰素基因刺激因子通路在柯萨奇病毒A6型感染手足口病患儿的表达及其临床意义[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(03): 135-141.
[4] 张雨, 杨松. 世界卫生组织《慢性乙型肝炎预防、诊断、关怀及治疗指南(2024年版)》解读[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(03): 129-134.
[5] 白若靖, 郭军. 肺炎克雷伯菌肺炎与干扰素信号通路关系研究进展[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(02): 71-74.
[6] 陈观梅, 左璇, 廖宝林. 慢性乙型肝炎新型免疫治疗研究进展[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(01): 7-10.
[7] 陈冬丽, 邓迎丽, 毕婧. α-干扰素治疗急性呼吸道病毒感染对Th1/Th2平衡及肺功能的影响[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 590-594.
[8] 顾玲, 赵颖, 伯雪, 王霞, 张扬, 李琼, 杨永静, 褚玲玲. 布地奈德联合干扰素雾化吸入治疗对病毒性肺炎的临床疗效[J/OL]. 中华肺部疾病杂志(电子版), 2023, 16(05): 727-728.
[9] 席素雅, 商焕霞, 贺向红, 张玲, 郑立恒, 乔庆哲, 刘薇. IL-27、IFN-γ、IGRA、ADA在结核性胸腔积液中的表达[J/OL]. 中华肺部疾病杂志(电子版), 2023, 16(05): 664-666.
[10] 陈静, 张春明, 周斌, 吴明明. 甲苯磺酸瑞马唑仑联合瑞芬太尼全身麻醉对胸腔镜肺叶切除患者术后应激反应及血清PAF、γ干扰素的影响[J/OL]. 中华肺部疾病杂志(电子版), 2023, 16(04): 554-556.
[11] 朱迎, 赵征, 许达, 陆录, 殷保兵. 免疫检查点抑制剂治疗肝细胞癌的进展与展望[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 5-10.
[12] 刘一, 文旖旎, 吴映辉. 过敏性紫癜患儿外周血辅助性T细胞、调节性T细胞细胞因子与肾损害的相关性分析[J/OL]. 中华肾病研究电子杂志, 2023, 12(05): 271-275.
[13] 胡静, 杨秀锦, 侯志云. HBV感染患者外周血ISGs表达水平变化及其与干扰素治疗疗效的关系[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(04): 343-347.
[14] 徐韫健, 吴柳, 尹小毛. 结核病γ-干扰素释放试验假阴性的影响因素分析[J/OL]. 中华临床实验室管理电子杂志, 2024, 12(02): 75-79.
[15] 牛红霞, 毛月然, 陈琦琪, 胥俊越, 董静, 王振, 杨彦娜, 张明. 可溶性程序性死亡受体-1及其配体和干扰素-γ在急性冠脉综合症患者血清中的表达特征和临床意义[J/OL]. 中华卫生应急电子杂志, 2024, 10(01): 10-15.
阅读次数
全文
0
HTML PDF
最新录用 在线预览 正式出版 最新录用 在线预览 正式出版
0 0 0 0 0 0


摘要
38
最新录用 在线预览 正式出版
0 0 38
  来源 本网站 其他网站
  次数 21 17
  比例 55% 45%