目的:了解抗病毒治疗后慢性丙型肝炎(CHC)患者外周血 Treg 比例及其表面程序性坏死因子‐1(PD‐1)和 TGF‐β表达水平的变化。方法2012年10月至2013年10月郑州大学第一附属医院感染科 CHC 患者86例,均经聚乙二醇干扰素α‐2a(Peg IFNα‐2a)联合利巴韦林(RBV)治疗,健康对照组为30名健康体检者。流式细胞仪检测 CHC 患者抗病毒治疗后,获得快速病毒学应答(RVR)、早期病毒学应答(EVR)和治疗结束时病毒学应答(ETVR)、获得持续病毒学应答(SVR)和未获得 SVR 患者外周血 Treg 比例及其表面 PD‐1和 TGF‐β表达水平。统计学处理采用 t 检验。结果86例 CHC 患者抗病毒治疗后获得 RVR 29例,EVR 67例,ETVR 79例;随访24周时获得 SVR 67例。健康对照组Treg 比例为2.18+0.65,CHC 组为10.31+5.61,差异有统计学意义(t =2.28,P<0.05)。1b 基因型患者外周血 Treg 比例在基线、获得 RVR 、EVR 和 ETVR 时分别为14.44±3.78、11.01±1.79、8.24±2.98和5.36±1.47;2a 基因型患者外周血 Treg 比例在基线、获得 RVR 、EVR 和 ETVR 时分别为12.34+2.82、8.99±1.68、7.53±2.96和4.79+1.23,呈逐渐下降趋势。 Treg 表面 PD‐1和TGF‐β的表达也呈下降趋势。获得 SVR 和未获得 SVR 患者的基线 PD‐1分别为29.11±14.65和37.73±11.65(t=2.15,P=0.04);TGF‐β分别为41.20±18.96和56.75±14.42(t=2.66,P<0.01)。治疗结束后随访24周时,PD‐1分别为10.36±4.81和36.46±10.52(t=13.95,P<0.01);TGF‐β分别为10.06±4.64和45.23±17.85(t=11.85,P <0.01)。结论抗病毒治疗后 CHC 患者外周血 Treg 比例及其表面PD‐1和 TGF‐β分子的表达水平均明显下降,动态检测上述指标可预测抗病毒治疗效果。
Objective To investigate the dynamic changes of regulatory T cells (Treg ) and the surface expression of programmed death (PD)‐1 and the level of transforming growth factor (TGF )‐βduring antiviral treatment in patients with chronic hepatitis C (CHC) .Methods Eighty‐six CHC patients referred to the First Affiliated Hospital of Zhengzhou University from October 2012 to October 2013 were included ,and all of them were administered with pegylated interferon α‐2a and ribavirin .Thirty healthy controls were enrolled .The percentage of Treg cells ,PD‐1 expression and TGF‐β level were analyzed by flow cytometry at baseline and at time of achieving rapid virological response (RVR ) , early viral virological (EVR ) , end‐of‐treatment virological response (ETVR ) and sustained virological response (SVR) ,or not achieving SVR .Comparison between two groups was analyzed by t test .Results Among 86 CHC patients ,the proportions of RVR ,EVR ,ETVR ,and SVR at week 24 of follow‐up were 29 cases ,67 cases ,79 cases and 67 cases ,respectively .Percentage of Treg cells in CHC patients was much higher than that in healthy controls (10 .31 ± 5 .61 vs 2 .18 ± 0 .65 ,t = 2 .28 , P〈 0 .05) .During antiviral therapy ,percentages of Treg cells declined ,not only in CHC patients with HCV genotype 1b (at baseline , RVR ,EVR ,and ETVR :14 .44 ± 3 .78 ,11 .01 ± 1 .79 ,8 .24 ± 2 .98 ,and 5 .36 ± 1 .47 ,respectively ) ,but also in those infected with HCV genotype 2a (at baseline ,RVR ,EVR ,and ETVR :12 .34 ± 2 .82 ,8 .99 ± 1 .68 ,7 .53 ± 2 .96 ,and 4 .79 ± 1 .23 ,respectively ) .Expressions of PD‐1 and TGF‐β also decreased .At baseline ,the expressions of PD‐1 in patients with SVR and without SVR were 29 .11 ± 14 .65 and 37 .73 ± 11 .65 ,respectively (t = 2 .15 , P = 0 .04) ,and the levels of TGF‐β were 41 .20 ± 18 .96 and 56 .75 ± 14 .42 ,respectively (t= 2 .66 ,P〈 0 .01) .At week 24 ,the expressions of PD‐1 in patients with SV