长效干扰素α-2a治疗慢性乙型肝炎过程中外周血浆样树突状细胞的变化及其与疗效的关系

Clinical profiles of circulating plasmacytoid dendritic cells in chronic hepatitis B patients in response to pegylated-interferon alfa-2a treatment

目的 观察长效干扰素（PEG-IFN α-2a）治疗慢性乙型肝炎过程中外周血浆样树突状细胞（pDC）亚群的变化及其与临床疗效的关系. 方法 41例慢性乙型肝炎患者接受PEG-IFN α-2a（180 μg）每周皮下注射一次,治疗48周;治疗过程中检测肝功能、血清HBV病毒学标志物和HBVDNA,在治疗前及治疗开始后2、12、24、36、48周分别检测外周血pDC数量和功能及Toll样受体（TLR）9的表达水平、血清肿瘤坏死因子（TNF）α及IFN γ水平.对数据进行成组设计t检验、非参数检验、重复测量资料的方差分析. 结果 应答组与无应答组比较,TLR9平均荧光强度、pDC数量及INF α分泌能力在治疗2周时均明显下降,应答组在12周时TLR9平均荧光强度恢复（66.25±13.10）,无应答组仍处于低水平（51.47±16.85）,差异有统计学意义（t=2.478,P＜0.05）;12周时应答组pDC数量恢复（5.24±1.61）,无应答组为（3.74±1.25）,差异有统计学意义（t=2.644,P＜0.05）;12周时应答组IFN α分泌能力明显升高（459.94±200.27） pg/ml,显著高于无应答组[（237.18± 123.57）pg/ml],差异有统计学意义（t=2.942,P＜0.05）.治疗24周时,应答组血清IFN γ水平明显升高[（67.81±16.64） pg/ml],显著高于无应答组[（43.73± 15.97） pg/ml],差异有统计学意义（t=3.396,P＜ 0.05）;TNFα水平为[（268.94±64.32）pg/ml],也显著高于无应答组[（206.45±78.28） pg/ml],差异有统计学意义（t=2.22,P＜0.05）.结论 pDC在PEG-IFNα-2a治疗诱发的早期免疫应答中发挥重要作用,抗病毒治疗过程中pDC数量和功能的恢复可能是机体抗病毒治疗应答的重要因素.

Objective To investigate the changes in circulating plasmacytoid dendritic cells （pDCs） in patients with chronic hepatitis B （CHB） during the course of treatment with pegylated-intefferon alfa-2s （peg-IFNα-2a） and to determine the correlations with therapeutic response.Methods Forty-one patients with CHB who were receiving peg-IFNα-2a antiviral treatment for 48 weeks were enrolled in the study.Expression of the Toll-like receptor 9 （TLR9） on and frequency and functionality of the pDCs were analyzed at treatment weeks 0,2,12,24,36 and 48.Results All patients exhibited an initially rapid decrease in the numbers of circulating pDCs and showed CpG-induced endogenous IFNα production within the first 2 weeks of treatment.Subsequently,all responders displayed a continuous increase in pDC numbers as well as functionality,both of which peaked around week 12 of treatment; in addition,these treatment responses were accompanied by significantly increased levels of type 1 T helper cytokines （P ＜ 0.05）,which did not occur in the non-responders.Conclusion pDCs are involved in the initial therapeutic immune response stimulated by peg-IFNα-2a treatment.Recovery of blood pDC number and functionality may represent a predictor of favorable response to peg-IFNα-2a antiviral treatment in patients with CHB.