Th17/Treg比率在慢性乙型肝炎患者外周血的动态变化及意义

摘要

目的:通过比较不同治疗方法对慢性乙型肝炎(Chronic hepatitis B ,CHB)患者外周血Th17(T helper lymphocyte 17)、Treg(regular T cell)细胞频率及Th17/Treg比率的变化,探讨其在CHB患者疾病转归中的意义.方法:CHB患者40例,根据保肝治疗基础上是否加用核苷酸抗病毒药物分为未抗病毒治疗组(Chronic hepatitis B without antiviral,CHBWA)20例、抗病毒治疗组(Chronic hepatitis B antiviral,CHBA)20例、乙肝病毒携带者(Asymptomatic hepatitis B carriers ,AsC)10例、健康对照组(Health control,HC)10例;采用流式细胞术检测CHBWA组0月、1月及CHBA组0月、1月、3月,AsC患者和HC外周血Th17、Treg细胞频率,计算Th17/Treg比率,观察其在疾病不同阶段的动态变化.结果:CHBWA组保肝治疗1月后,Th17/Treg比率(0.39±0.11)比0月(1.20±0.26)明显降低(P<0.01),已接近AsC组(0.39±0.14)及HC组(0.42±0.20)Th17/Treg比率水平(P>0.05),且Th17/Treg比率与ALT有良好的正相关关系(r=0.709,P=0.000);在CHBA组,Th17/Treg比率在1月(0.73±0.32)、3月(0.76±0.44)均较0月(1.18±0.27)明显下降,与0月比较差异有统计学意义(P<0.01),但继续治疗到3月时Th17/Treg比率较1月时变化不明显,Th17/Treg比率在0、1、3月均高于AsC组及HC组(P<0.01,0.05);Th17/Treg比率与ALT、HBV DNA有良好的正相关关系(r=0.500,P=0.000;r=0.345,P=0.007);两组间比较,0月时两组间Th17/Treg比率差异无统计学意义(P>0.05),但经治疗1月后CHBA组Th17/Treg比率高于CHBWA组(t=4.471,P<0.01).结论:CHB患者中,抗病毒治疗将迅速影响Th17、Treg细胞频率,导致Th17/Treg比率的变化,其变化可能与清除病毒有关.%Objective:To investigate the significance of T helper type 17 cells(Th17)/T regulatory cells (Treg) in the prognosis of chronic hepatitis B(CHB) by comparing the changes of Th17 cells ,Treg cells and their rate under different therapy in chronic hepatitis B patients.Methods: 40 patients infected with chronic hepatitis B(CHB) were divided into chronic hepatitis B without antiviral(CHBWA) group and chronic hepatitis B antiviral(CHBA) group depending on whether nucleoside antiviral was applied,with 20 cases each,10 cases in asymptomatic hepatitis b carriers(AsC) group.10 cases in health control (HC) group.Flow cytometer(FCM) was adopted to detect peripheral blood Th17 and Treg cell frequency in CHB patients at 0,1 month in CHBWA group ,at 0,1,3 month in CHBA group,AsC patients and HC cases ,then calculating Th17/Treg ratio and observing the dynamic changes at different disease states.Results: After the liver-protecting treatment in CHBWA patients,the Th17/Treg ratio at 1 month(0.39±0.11)decreased compared to 0 month(1.20±0.26)rapidly(P<0.01),and the ratio nearly reached the level of AsC and HC group (P>0.05).Ratio of Th17/Treg and ALT had good positive correlation (r=0.709,P=0).In CHBA patients group,after the liver-protecting and antiviral treatment,patients′ Th17/Treg ratio decreased rapidly in the first month(0.73±0.32) and third month(0.76±0.44),and there′s statistical difference compared with 0 month(1.18±0.27,P<0.01),but there was no significant change of Th17/Treg ratio after being treated for 3 months compared with 1 month,and the Th17/Treg ratios at 0,1,3 month were higher than that in AsC group and HC group(P<0.01).Ratio of Th17/Treg and ALT have good positive correlation (r=0.500,P=0.000),also the ratio of Th17/Treg and HBV DNA were positively correlated (r=0.345,P=0.007).Comparison of peripheral blood Th17,Treg cells frequency,Th17/Treg ratio between CHBWA and CHBA group at 0 month had no statistical significance(P>0.05),while the Th17/Treg ratio in CHBA group was higher than CHBWA group(t=4.471,P<0.01) after 1 month of treatment.Conclusion: In the CHB patients,antiviral treatment will influence the Th17,Tregs cells frequency,resulting the change of Th17/Treg ratio,but also the ratio may be associated with virus removal.