慢性乙型肝炎患者NK细胞功能与干扰素疗效相关性研究  

Functions of NK cells in chronic hepatitis B patients treated with interferon

作　　者：屈晓晶 路遥 曹卫华 张英 冉崇平 齐天林 胡蕾苹 郝红晓 张璐 李明慧 谢尧 Qu Xiaojing Lu Yao Cao Weihua Zhang Ying Ran Chongping Qi Tianlin Hu Leiping Hao Hongxiao Zhang Lu Li Minghui Xie Yao(Second Division of Liver Center, Beijing Ditan Hospital, Capital Medical University Beifing 100015, China)

机构地区：[1]首都医科大学附属北京地坛医院肝病中心肝病二科,北京100015

出　　处：《中华实验和临床病毒学杂志》2017年第4期333-337,共5页Chinese Journal of Experimental and Clinical Virology

基　　金：北京市医院管理局临床技术创新项目（XMLX201706）

摘　　要：目的 探讨慢性乙型肝炎（Chronic hepatitis B,CHB）患者外周血NK细胞频数及功能分子与干扰素α（Interferon-alpha,IFNα）疗效的相关性.方法 采集乙型肝炎病毒（Hepatitis B virus,HBV）慢性感染免疫清除（Immune clearance,IC）期经聚乙二醇干扰素α-2a（Peg-IFNα-2a）治疗患者在基线及治疗12和24周静脉全血,采用流式细胞仪检测外周血CD3-CD56＋ NK细胞、CD56brightNK细胞和CD56dimNK细胞频数及NK细胞表面受体IFNAR2和NKp46的表达.血浆HBV DNA、HBsAg、HBeAg含量及肝功能由北京地坛医院检验科提供.结果 本实验共入组41例IC期经Peg-IFNα-2a治疗患者,包括21例应答不佳（Poor response,PG）患者和20例应答（Good response,GR）患者,结果显示：与基线比较,GR组CD3-CD56＋NK细胞频数在治疗24周升高（11.74,5.69％ - 18.15％ vs 13.7,9.36％ -20.18％,P〉0.05）,在PR组同样升高（8.94,6.26％ -14.15％ vs 12.5,7.64％-16.55％,P〉0.05）.GR组CD56brightNK细胞频数在治疗24周显著升高（9.49,6.2％-12.48％vs 12.98,7.75％ -20.93％,P〉0.05）,在PR组也同样显著升高（11.45,8.27％ -19.13％ vs 17.52,12.3％ - 22.42％,P=0.0239）.GR组NK细胞NKp46表达水平在治疗24周显著升高（90.55,83.8- 94.78 vs 93.8,92.28 - 96.4,P=0.0263）,而PR组却未升高（95,90.6 - 96.15 vs 94.3,92.1-95.6,P〉0.05）.GR组NK细胞NKp46high表达水平在治疗24周显著升高（12.4,8.58- 19.08 vs 39.3,23.15-49.3,P=0.0011）,其升高幅度显著高于PR组（14.2,9.78 - 17.65 vs 27.58,19.13 -36.56,P=0.006）.结论 慢性乙型肝炎患者经Peg-IFN-α-2a治疗后外周血CD3-CD56＋ NK细胞和CD56bright NK细胞频数升高,对Peg-IFN-α-2a治疗应答患者NK细胞上NKp46表达上调,而且Peg-IFN-α-2a治疗使NKp46high表达显著上调,尤其在应答患者.Objective To elucidate the functions of peripheral blood NK cells in chronic hepatitis B patients treated with interferon.Methods Venous whole blood samples were obtained from patients in the immune clearance （IC） phase treated with peg-interferon-alpha-2a （Peg-IFNo-2a） at baseline （t =0）,12 weeks （t =12） and 24 weeks （t =24）.The frequencyies of peripheral blood CD3-CD56 ＋ NK cells,CD56brightNK cells and CD56dim NK cells,the expression level of IFNAR2 and NKp46 on NK cells were detected by flow cytometry.The levels of serum HBV DNA,HBsAg,HBeAg and ALT were detected by Ditan Hospital clinical laboratory.Results Forty-one patients in the IC phase treated with Peg-IFNα-2a,including 21 poor response （PR） patients and 20 good response （GR） patients,were recruited for this study.Theresult were as follows：The frequency of peripheral blood CD3-CD56 ＋ NK cells was increased at week 24 in GR compared with the baseline（11.74,5.69%-18.15% vs 13.7,9.36-20.18%,P 〉0.05）,and it also was increased in PR（8.94,6.26%-14.15% vs 12.5,7.64-16.55%,P 〉0.05）.The frequency of peripheral blood CD56brightNK cells was increased at week 24 in GR compared with the baseline （9.49,6.2%-12.48% vs 12.98,7.75%-20.93%,P〉0.05）,and it also was increased in PR（11.45,8.27%-19.13% vs 17.52,12.3%-22.42%,P =0.0239）.The expression level of NKp46 on NK cells was significantly increased at week 24 in GR compared with the baseline （90.55,83.8-94.78 vs 93.8,92.28-96.4,P =0.0263）,but it was not increased in PR（95,90.6-96.15 vs 94.3,92.1-95.6,P 〉0.05）.The expression level of NKp46high on NK cells was significantly increased at week 24 in GR compared with the baseline（12.4,8.58-19.08 vs 39.3,23.15-49.3,P =0.0011）,at that range of the increase was significantly higher than PR （14.2,9.78-17.65 vs 27.58,19.13-36.56,P =0.006）.Conclusions The frequencies of peripheral blood CD3-CD56 ＋ NK cells and CD56bright NK cells were increased from patients in the IC phase treated with Peg-IFNα-2a.The exp

关 键 词：肝炎病毒 乙型 自然杀伤细胞 免疫病理 干扰素Α 

分 类 号：R512.62[医药卫生—内科学]