慢性乙型肝炎患者不同免疫状态及抗病毒治疗早期外周血NK细胞亚群变化特点  

Characteristics of peripheral blood natural killer cell subsets in patients with chronic hepatitis B during the early phase of antiviral treatment

作　　者：潘志耘 曹淑凤[1] 黄睿[2] 王贵阳[2] 田辰[2] 吴超[1] 

机构地区：[1]南京医科大学鼓楼临床医学院感染科,江苏南京210008 [2]南京大学医学院鼓楼医院感染科

出　　处：《胃肠病学和肝病学杂志》2017年第4期444-448,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家自然科学基金(81470093);江苏省临床医学科技专项(BL2012034);江苏省医学领军人才与创新团队资助项目(LJ201154)

摘　　要：目的观察慢性乙型肝炎(chronic hepatitis B,CHB)患者不同免疫状态下外周血NK细胞亚群特点,比较聚乙二醇干扰素及核苷(酸)类似物抗病毒治疗早期外周血NK细胞亚群变化差异。方法收集门诊不同免疫状态下的CHB患者81例,其中免疫耐受期(immune-tolerance phase,IT)患者22例,免疫活化期(immune-activation phase,IA)患者52例,非活动携带组(inactive carry phase,IC)7例,同时纳入健康志愿者(healthy controls,HC)39例作为对照。对27例符合抗病毒治疗标准的患者进行抗病毒治疗,并完成随访。其中22例采用核苷(酸)类似物治疗,5例采用聚乙二醇干扰素治疗。流式细胞术检测患者抗病毒治疗0周、4周、8周、12周及24周外周血NK细胞亚群的比例。结果免疫耐受组、非活动携带组NK细胞总数较健康对照组明显上升(P<0.05)。非活动携带组CD56^(dim)NK细胞比例较健康对照组升高(P=0.02)。免疫耐受组及免疫活化组患者外周血CD56^(bright)NK细胞以及CD56^(bright)/CD56^(dim)NK比值与健康对照组相比均明显升高(P<0.05);比较CHB患者聚乙二醇干扰素及核苷(酸)类似物抗病毒治疗各时间点外周血NK亚群比例发现,CD56^(dim)NK细胞比例无明显差异。聚乙二醇干扰素组CD56^(bright)NK细胞比例在8周、12周、24周时明显高于核苷(酸)类似物组,差异有统计学意义(P<0.05)。结论外周血NK细胞亚群可能与慢性HBV持续感染相关。在抗HBV治疗过程中,聚乙二醇干扰素可能通过上调CD56brightNK细胞发挥免疫调节作用。Objective To observe the characteristics of peripheral blood natural killer （NK） cell subsets in patients with chronic hepatitis B （CHB） during different immune status, and to compare the changes of peripheral blood NK cell subsets during early phase of antiviral treatment by pegylated interferon-α （PEG-IFN-α） or nucleos （t） ide analogues （NAs）. Methods Eighty-one patients with CHB including 22 patients in immune-tolerance phase （IT）, 52 patients in immune-activation phase （IA） and 7 patients in inactive carry phase （IC）. Thirty-nine healthy volunteers were included as healthy controls （HC）. Twenty-seven patients underwent antiviral therapy and were followed for 24 weeks. Twentytwo patients were treated with NAs and 5 patients were treated with PEG-IFN-α. The proportion of peripheral blood NK cells subsets were assessed at five time points of antiviral therapy： 0 weeks, 4 weeks, 8 weeks, 12 weeks and 24 weeks by flow cytometry. Results The proportion of peripheral blood NK cells in IT and IC groups were markedly increased than that in healthy controls （P 〈 0.05） ; The proportion of CD56dim NK cells in IC group was higher than those in HC （P = 0.02）. The proportion of CD56bright NK cells and CDN6brisht/CD56alto NK ratio in IT and IA were higher than those in HC （P 〈 0. 05） ; there was no significant difference about the proportion of CD56aim NK cells between PEG-IFN-α group and NAs group. The CD56brisht NK cells of PEG-IFN-α group were higher than those in NAs group at 8 weeks, 12 weeks and 24 weeks （P 〈 0.05）. Conclusion The peripheral blood NK cells subsets may be associated with chronic HBV persistency. The PEG-IFN-α may play a role in immune regulation by up-regulating the proportion of CD56brisht NK ceils during the antiviral treatment of CHB.

关 键 词：慢性乙型肝炎 自然杀伤细胞亚群 抗病毒 

分 类 号：R575.1[医药卫生—消化系统]