HBeAg阳性慢性乙型肝炎患者外周血效应T淋巴细胞表面程序性死亡受体-1表达的研究  

Dynamic changes of PD-1 expression on CD4^＋and CD8^ ＋ T cells in patients with HBeAg-positive chronic hepatitis B treated with telbivudine

作　　者：李志勤[1] 张佳佳[1] 胡春玲[1] 平玉 李华[1] 闫婧雅[1] 吕君[1] 曾庆磊[1] 余祖江[1] 张毅[2] 

机构地区：[1]郑州大学第一附属医院感染科,450052 [2]郑州大学第一附属医院生物细胞治疗中心,450052

出　　处：《中华临床感染病杂志》2016年第6期486-490,共5页Chinese Journal of Clinical Infectious Diseases

基　　金：国家自然科学基金（81261120402、81171986、81302593）;河南省高等学校重点科研项目（15A320083）

摘　　要：目的探讨HBeAg阳性慢性乙型肝炎（CHB）患者CD4^＋和CD8^＋效应T淋巴细胞表面程序性坏死受体-1（PD-1）的表达与临床指标的关系及其在抗病毒治疗中的变化。方法选择2013年1月至2014年6月在郑州大学第一附属医院感染科接受替比夫定抗病毒治疗的56例HBeAg阳性CHB患者，动态监测基线、抗病毒治疗24、48和72周时的PD-1水平。应用t检验比较不同ALT水平、HBV DNA水平及HBeAg转阴前后PD-1表达水平的差异，并采用完全随机方差分析比较PD-1在CD4^＋和CD8^＋效应T淋巴细胞表面水平的差异。结果治疗基线，CD4^＋和CD8^＋效应T淋巴细胞表面的PD-1表达水平在丙氨酸转氨酶（ALT）〈90 U/L组均显著高于ALT≥90 U/L组的患者（t＝12.20和9.69，P值均〈0.01）；而HBV DNA≥5lgIU/mL组患者的CD4^＋和CD8^＋效应T淋巴细胞表面PD-1表达水平显著高于HBV DNA〈5 lgIU/mL组患者（t＝4.39和4.85，P值均〈0.01）。在基线、抗病毒治疗24、48及72周时，CD4^＋和CD8^＋效应T淋巴细胞表面的PD-1表达水平均呈进行性下降（F＝6.98和8.97，P〈0.01）。获得HBeAg转阴的CHB患者CD4^＋和CD8^＋效应T淋巴细胞表面PD-1表达水平较基线均显著降低（t＝18.45和18.01，P值均〈0.01）。结论HBeAg阳性CHB患者经替比夫定抗病毒治疗后，CD4^＋及CD8^＋效应T淋巴细胞表面的PD-1表达水平呈进行性下降，获得HBeAg转阴患者的PD-1水平较基线显著降低，提示获得HBeAg转阴患者体内免疫抑制状况出现改善。Objective To investigate the expression of PD-1 on CD4 ^＋ and CD8 ^＋ T cells in patients with HBeAg-positive chronic hepatitis B（CHB） treated with telbivudine. Methods Fifty-six HBeAg-positive CHB patients admitted in the First Affiliated Hospital of Zhengzhou University during January 2013 and June 2014 were enrolled in this study. The expression of PD-1 on CD4 ＋ and CD8 ＋ T cells was detected with flow cytometry at baseline, 24, 48 and 72 wks after telbivudine treatment. The relationship of PD-1 expression with alanine aminotransferase （ALT） level, HBeAg seroconversion and HBV DNA loads was analyzed, t test and completely random variance analysis were used to analyze the data. Results The PD-1 expression on CD4 ＋ and CD8 ^＋ T cells at baseline was higher in patients with low ALT levels compared to those with high ALT levels（t = 12.20 and 9.69,both P 〈0.01 ） ,while higher levels of PD-1 expression was also observed in patients with high HBV DNA load （≥5 lgIU/mL） compared to those with low HBV DNA load （t = d. 39 and 4.85, both P 〈 0.01）. PD-1 levels on CD4 ＋ and CD8 ^＋ T cells presented a declining trend after telbivudine treatment（ F = 6. 98 and 8.97, both P 〈 0.01 ）, PD-I expression in patients with HBeAg seroconversion showed lower levels compared with baseline values （t = 18.45 and 18.01, both P 〈0.01 ）. Conclusion In HBeAg-positive CHB patients, the expression of PD-1 on CD4 ^＋ and CD8 ^＋ T lymphocytes shows a decreasing trend during the treatment with telbivudine, indicating that antiviral therapy may alleviate the immunosnppression in these patients.

关 键 词：肝炎 乙型 慢性 抗病毒药 替比夫定 T淋巴细胞 程序性死亡受体一1 

分 类 号：R51[医药卫生—内科学]