慢性乙型肝炎患者核苷（酸）类似物治疗前后外周血中Treg和Thl7细胞及其相关细胞因子水平的变化  

Changes of Treg cells, Thl7 cells and Treg/Thl7 cell-associated cytokines in the peripheral blood ofpatients with chronic hepatitis B before and after nucleos （t）ide analogues antivirus therapy

作　　者：郭如意[1] 余雪平[1] 黄绿叶[1] 苏密龙[1] 明德松[1] 邓勇[1] 林振忠[1] 苏智军[1] 

机构地区：[1]福建医科大学附属泉州第一医院感染科,泉州362000

出　　处：《中华微生物学和免疫学杂志》2013年第3期216-221,共6页Chinese Journal of Microbiology and Immunology

基　　金：福建省医学创新课题（2012-cx-33）;泉州市科技计划项目资助课题（2011263）;泉州市科技计划项目（2008236）

摘　　要：目的观察慢性乙型肝炎（CHB）患者应用核苷（酸）类似物（NA）抗病毒治疗前后外周血中Treg、Thl7细胞及其相关细胞因子水平的变化。方法采用流式细胞术，检测44例NA治疗12周的CHB患者外周血Treg（CD4＋CD25highCDl27low）和Thl7（CD3＋CD8-IL-17＋）细胞频率。ELISA检测血清IL-10、TGF-[31、IL-17及IL-23水平。各组间采用Mann—WhitneyU检验，治疗前后采用Wile．oxon配对r检验。结果完全应答的14例患者的Treg细胞频率、IL-10、TGF．[31和IL-23水平及Treg／Thl7比率较治疗前明显下降（z=-2．691，-2．417，-2．237，-2．291，-2．291，P均〈O．05），Th117细胞频率及IL-17水平略有增加。部分应答的11例患者的Treg细胞频率、IL．10、TGF．[31和IL-23水平较治疗前明显下降（z=-1．988，-2．934，-2．756，-2．803，P均〈0．05），Thl7细胞频率及IL-17水平略有增加，Treg／Thl7比率略有下降。无应答的15例患者的Treg和11117细胞频率、IL．10、TGF．[31、IL-23、IL-17水平及Treg／Thl7比率较治疗无明显变化。HBVDNA下降I〉2log拷贝／ml及AIJT恢复正常时，Treg细胞频率与细胞因子IL-10、TGF—B1和IL-23水平较治疗前明显下降（P均〈O．05）。Treg细胞频率与HBVDNA及ALT水平三者之间具有-定的相关性。结论NA抗病毒治疗前后，CHB患者Treg和Thl7细胞频率及IL-10、TGF-[31、IL-23、IL-17水平均发生变化；治疗后获得满意应答的CHB患者Treg细胞频率、IL-10、TGF—B1、IL-23水平及Treg／Thl7比率明显下降，Thl7细胞及IL-17水平继续上升；且以上变化与病毒学应答及生化学应答有关。Objective To explore the relationship between the efficacy of nucleos （t） ide analogues antivirus therapy and changes of Treg ceils, Th17 cells and their associated cytokines in the peripheral blood of patients with CHB. Methods Forty-four CHB patients treated for 12 weeks were enrolled in this study. The frequencies of Treg ceils （CD4＋CD25highCD1271low T cells） and Thl7 cells （CD3＋CD8-IL-17＋ T cells） in the peripheral blood were assessed by flow cytometric analysis. Treg/Thl7 cell-associated cytokines IL- l0, TGF-β1, IL-17 and IL-23 levels were measured by enzyme-linked immunosorbent assay （ELISA）. The comparisons of overall means within groups and between before and after therapy were done by Mann-Whitney U test or Wilcoxon matched paired T test. Results In 14 complete-responders of 44 CHB patients, the frequencies of Treg cells, the levels of IL-10, TGF-I31 and IL-23 and Treg/Thl7 ratio were decreased signifi- cantly after nucleos（t） ide analogues antivirus therapy （Z=-2.691, -2. 417, -2. 237, -2.291, -2.291, both P〈0.05） , while the frequencies of Thl7 cells and the IL-17 levels were increased slightly. In 11 patrial-responders, the frequencies of Treg cells, the levels of IL-10, TGF-IM and IL-23 were decreased significantlv after nucleos（t）ide analomaes antivirus therapy （Z=-1. 988, -2. 934, -2.756, -2. 803, both P〈0.05） ; The frequencies of Thl7 cells and the IL-17 levels were increased slightly, while Treg/Th17 ratio was slightly decreased. In 15 non-responders, the frequencies of Treg cells, Thl7 cells, the levels of IL-10, TGF-~I, IL-17 and IL-23 and Treg/Thl7 ratio were not changed significantly after nucleos（t） ide analogues antivirus treatment. Either HBV DNA decrease at least 2 log copies/m1 or ALT normal, the frequencies of Treg ceils, the levels of IL-10, TGF-~I and IL-23 were decreased significantly （all P〈0.05）. The frequen- cies of Treg cells were positively correlated with HBV DNA and ALT, and the level of HBV DNA were corre- lated with ALT.

关 键 词：慢性乙型肝炎 TREG细胞 TH17细胞 核苷(酸)类似物 细胞因子 

分 类 号：R512.62[医药卫生—内科学]