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

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CD56dim 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CD56brightNK细胞以及CD56bright/CD56dim 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,CD56dim NK细胞比例无明显差异.聚乙二醇干扰素组CD56bright 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CD56bright NK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 CD56bright/CD56dim NK ratio in IT and IA were higher than those in HC (P ＜ 0.05);there was no significant difference about the proportion of CD56dim NK cells between PEG-IFN-α group and NAs group.The CD56bright 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 CD56bright NK cells during the antiviral treatment of CHB.