摘要
目的探讨使用直接抗病毒药物(direct-acting antivirals,DAAs)治愈的初治型慢性丙型肝炎(chronic hepatitis C,CHC)患者的T细胞免疫学特点及变化。方法选择2015年9月-2017年1月中国人民解放军总医院第五医学中心(原解放军第三〇二医院)采用达拉他韦(daclatasvir,DCV)和阿舒瑞韦(asunaprevir,ASV)治愈的13例初治型CHC患者为研究对象,13例健康者为健康对照组。采用流式细胞术检测健康者以及CHC患者治疗前、治疗第24周及治疗结束后(随访第4周、第12周、第24周)外周血中T细胞的表型和功能特征。结果与健康对照组相比,CHC患者治疗前T细胞、CD4^+T细胞及CD8^+T细胞PD1的表达显著增高(P均<0.05);T细胞及CD8^+T细胞CD3ζ平均荧光强度(mean fluorescence intensity,MFI)明显降低(P均<0.05);CD4^+T细胞CD3ζMFI降低,但差异无统计学意义(P>0.05)。与治疗前相比,DCV/ASV治疗第24周时及随访期,CHC患者外周血T细胞及CD4^+T细胞、CD8^+T细胞的频率、PD1的表达、CD3ζMFI均无明显变化;效应记忆型T细胞在总T细胞、CD4^+T细胞及CD8+T细胞中的比例无明显变化;CD8^+T细胞中CXCR5^+CD8^+T比例有增高趋势,但差异无统计学意义(P均>0.05)。结论DCV/ASV治愈的初治型HCV-1b型CHC患者,外周血T细胞表型和功能未发生显著改善。
Objective To explore the immunological features and changes of T cells in treatment-naive patients with chronic hepatitis C(CHC)who are cured by direct-acting antivirals(DAAs)therapy.Methods Thirteen treatment-naive CHC patients were included in this study,they were cured by daclatasvir and asunaprevir(DCV/ASV)in Fifth Medical Center of Chinese PLA General Hospital(formerly 302 Hospital of Chinese PLA)from September 2015 to January 2017.Meanwhile,thirteen healthy individuals were enrolled as healthy control group.Flow cytometry was applied to detect the phenotypic and functional characteristics of peripheral blood T cells in the population from 2 groups and in CHC patients before treatment,at 24 weeks of therapy,and after the end of therapy(Week 4,Week 12 and Week 24 during follow-ups).Results Compared with healthy control group,the levels of PD1 expression on peripheral blood T cells,CD4^+T cells,CD8^+T cells in CHC patients before treatment were significantly higher(P<0.05).CD3ζmean fluorescence intensity(MFI)on peripheral blood T cells and CD8^+T cells in CHC patients before treatment were obviously lower(P<0.05).CD3ζMFI on peripheral blood CD4^+T cells was decreased without statistical difference(P>0.05).Compared with before treatment,the frequencies,the expression levels of PD1,CD3ζ MFI of peripheral blood T cells,CD4^+T cells and CD8^+T cells showed no obvious change at the end of DCV/ASV therapy and during follow-up period.The proportion of effector memory T cells in peripheral blood T cells,CD4^+T cells and CD8^+T cells showed no obvious change.The proportion of CXCR5+CD8^+T in CD8^+T cells increased,but there was no statistical difference(P>0.05).Conclusions In treatment-naive CHC patients of HCV 1 b genotype,cured by DCV/ASV,peripheral blood T cell phenotype and function are not improved significantly.
作者
史继静
周文靖
李元元
常文仙
贾晓燕
张纪元
王福生
SHI Ji-jing;ZHOU Wen-jing;LI Yuan-yuan;CHANG Wen-xian;JIA Xiao-yan;ZHANG Ji-yuan;WANG Fu-sheng(The Central Lab of Zhengzhou First People’s Hospital,450000,China)
出处
《传染病信息》
2020年第6期527-532,557,共7页
Infectious Disease Information
基金
河南省2018年科技发展计划项目(182102310594)
国家自然科学基金(81601731)。
