抗病毒治疗对慢性HBV感染者外周血中PD-1和PD-L1的影响及其与血清HBV-DNA的关系

发布时间：2018-08-12 17:24

【摘要】：目的探讨两种给药方案对慢性HBV感染者外周血中T淋巴细胞表面PD-1及其主要配体PDL1的影响,以及其与血清HBV-DNA的关系。方法 71例慢性HBV感染者按HBV-DNA载量不同分为3lg IU/m L、3~6 lg IU/m L和6 lg IU/m L 3组,进入疗程后按照给药不同分为:拉米夫定组(LAM组)23例,拉米夫定+阿德福韦酯联合治疗组(LAM+ADV组)48例,分别于治疗的0、12和24周时,采用流式细胞仪检测患者外周血中CD4+和CD8+T细胞表面PD-1、PD-L1的表达,ELISA法检测外周血中γ-干扰素(IFN-γ)的表达,同时检测HBV-DNA、肝功能、HBV血清学标志物等,并设立正常对照组26例。结果不同HBV-DNA载量患者的外周血中CD4+和CD8+T细胞表面PD-1、PD-L1的表达均明显高于正常对照组(P0.05),且与HBV-DNA载量呈正相关(P0.05),而IFN-γ水平均明显低于正常对照组(P0.05);抗病毒治疗后,两种治疗方案组患者的PD-1、PD-L1表达均有明显下降,除LAM组的CD4+PD-L1+外其他CD4+和CD8+T细胞表面的PD-1、PD-L1在治疗前与治疗12周和治疗24周均差异有统计学意义(P0.05),其中LAM+ADV组在降低的速度和幅度上均明显优于LAM组(P0.05);IFN-γ的表达逐渐升高,至治疗24周时升至(24.55±5.81)pg/m L,明显高于治疗前(13.97±4.13)pg/m L(P0.05),但两治疗组间差异无统计学意义(P0.05)。结论慢性乙型肝炎患者外周血中CD4+和CD8+T细胞表面PD-1、PD-L1的表达与HBV-DNA载量呈正相关,抑制HBV的复制可以有效地降低负性调控因子PD-1、PD-L1的表达;LAM+ADV联合治疗方案对PD-1、PD-L1降低的速度和幅度明显优于LAM的单一用药,更易提高T淋巴细胞的活性。
[Abstract]:Objective to investigate the effects of two administration regimens on PD-1 on T lymphocyte surface and its main ligand PDL1 in peripheral blood of patients with chronic HBV infection and the relationship between them and serum HBV-DNA. Methods Seventy-one patients with chronic HBV infection were divided into three groups according to their HBV-DNA load: 3lg IU/m L 3L 6 LG IU/m L and 6 LG IU/m L 3. After entering the course of treatment, they were divided into lamivudine group (LAM group) and lamivudine group (LAM group, 23 cases). 48 patients were treated with lamivudine adefovir ester (LAM ADV group). The expression of PD-1 and PD-L1 on CD4 and CD8 T cells in peripheral blood were detected by flow cytometry at 0 ~ 12 and 24 weeks after treatment. The expression of interferon 纬 (IFN- 纬) in peripheral blood was detected by Elisa. HBV-DNA, liver function and HBV serological markers were also detected, and 26 cases of normal control group were set up. Results the expression of PD-1 PD-L1 on peripheral blood of patients with different HBV-DNA load was significantly higher than that of normal control group (P0.05), and positively correlated with HBV-DNA load (P0.05), but IFN- 纬 level was significantly lower than that of normal control group (P0.05). The expression of PD-1 pPD-L1 was significantly decreased in both groups. There was significant difference in PD-1 PD-L1 on the surface of CD4 and CD8 T cells except for CD4 PD-L1 in LAM group (P0.05). The expression of IFN- 纬 in LAM ADV group was significantly higher than that in LAM group (P0.05), and there was a significant difference between the two groups before and after 12 weeks and 24 weeks of treatment (P0.05), and the expression of IFN- 纬 in LAM ADV group was significantly higher than that in LAM group (P0.05). At 24 weeks after treatment, it rose to (24.55 卤5.81) pg/m L, which was significantly higher than that before treatment (13.97 卤4.13) pg/m L (P0.05), but there was no significant difference between the two groups (P0.05). Conclusion the expression of PD-1 and PD-L1 on the surface of CD4 and CD8 T cells in patients with chronic hepatitis B is positively correlated with the HBV-DNA load. Inhibiting the replication of HBV could effectively reduce the expression of PD-1nPD-L1. The rate and amplitude of PD-1pPD-L1 decrease was obviously higher than that of LAM alone, and the activity of T lymphocytes could be increased more easily.
【作者单位】：江苏省常州市第三人民医院肝病研究所;
【基金】：江苏省常州市卫生局重大科技项目(编号:ZD201106)
【分类号】：R512.62

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