白细胞介素-21在慢性乙型肝炎病毒感染自然史不同阶段的表达分析

Expression and significance of IL-21 in patients infected with hepatitis B virus at different stages

目的:探讨白细胞介素(IL)-21在慢性乙型肝炎病毒(HBV)感染自然史不同阶段的表达情况及其与HBV-DNA、ALT的关系。方法:收集101例慢性HBV感染者(病例组)和25例对照者(对照组)的临床资料,流式细胞微球技术检测血清IL-21蛋白水平,并用real-time PCR法检测IL-21及IL-21受体(R)m RNA的表达情况。结果:(1)病例组分为免疫耐受期组(25例)、免疫清除期组(25例)、低复制期组(26例)及再活动期组(25例)。(2)病例组血清IL-21蛋白及m RNA水平均高于对照组(P<0.001);免疫清除期组及再活动期组血清IL-21蛋白及m RNA水平均高于对照组、免疫耐受期组及低复制期组(P<0.001);低复制期组血清IL-21蛋白水平高于对照组(P<0.001)及免疫耐受组(P=0.036)。(3)IL-21R m RNA水平在各组间没有差异。(4)血清IL-21蛋白与HBV-DNA载量呈负相关(r=-0.472,P=0.001)。(5)血清IL-21蛋白与ALT水平无关(r=0.024,P=0.868)。结论 :IL-21在慢性HBV感染者中表达上调,且与免疫活动有关,可能是机体控制HBV复制的机制之一。

Objective To determine the expression of interleukin-21 （IL-21） in patients infected with hepatitis B virus （HBV） and its association with HBV-DNA and ALT. Methods Clinical dates and blood specimen were collected from 25 unrelated healthy controls （HC） and 101 independent chronic HBV infected patients, including 25 patients in immune tolerant phase（IT）, 25 in immune clearance phase（IC）, 26 patients in inactive HBV carrier state （IA） and 25 patients in immune reactive phase （IR）. Serum IL-21 levels were measured by Cytometric Bead Array （CBA）. IL-21 mRNA and IL-21 receptor mRNA were measured by real-time PCR. Results Chronic HBV-infected patients had higher levels of serum IL-21 and IL-21 mRNA, with P 〈 0.001 for both. In subgroup analysis, both serum IL-21 and IL-21 mRNA levels in IC, IR were higher than those in IT, IA and HC （all P 〈 0.001）. Serum IL-21 level in IA was higher than that in HC and IT （P 〈 0.001, P = 0.036）. IL-21R mRNA levels were different between groups. Serum IL-21 level was associated with HBV-DNA （r = -0.472, P 〈 0.001）, but not with ALT. Conclusion IL-21, up-regulated in chronic HBV infection, is associated with immune activity and may play a key role in HBV control.