成人急性HBV感染后免疫指标的变化及不同转归的比较

The consequence of acute hepatitis B and change of immune markers in adult

目的观察成人急性HBV感染后免疫指标的变化并进行不同转归比较。方法选择29例急性乙肝患者和20例正常对照者,采用双抗体酶联分析法检测外周血细胞因子IL2、IFNγ、IL4、IL10和IL12的水平;通过流式细胞仪观察外周血T淋巴细胞亚群变化;采用抗人T淋巴细胞单克隆抗体间接免疫荧光法观察外周血T淋巴细胞膜IFNγ和IL4的表达。结果29例HBeAg全部转阴,8例HBsAg未转阴。在HBsAg转阴组,病程早期和中期血清IL2、IFNγ、IL4及IL12水平增高与正常组比P<0.05,中期IL4下降与早期比P<0.05,晚期IL2、IFNγ、IL4及IL12下降与中期比P<0.05;未转阴组各期IL4水平增高与正常组比P<0.05。转阴组早期Th1/Th2降低与对照组比P<0.05,未转阴组各期Th1/Th2降低与对照组比P<0.05。未转阴组中5例入院时HBVDNA<103且IFNγ水平明显低。两组CD4+/CD8+变化趋势不同。转阴组早期和中期IL4膜表达高于正常对照组,中期IL4表达低于早期,晚期IL4表达低于中期,P值均<0.05。未转阴组各期IL4表达高于正常对照组,P<0.05,各期之间IL4表达无统计学差异。结论IFNγ升高与疾病恢复相关。持续高水平的IL4表达易致慢性化。恢复Th1/Th2细胞的平衡可能是控制乙型肝炎慢性化的一条途径。CD4+/CD8+失调可能影响机体清除病毒的能力,导致感染的持续。

Objective To explore the natural consequence of acute hepatitis B in adult and chang of immune markers. Methods The serum levels of IL-2, IFN-γ, IL-4 ,IL-10 and IL-12, were measured by using enzymelinked immumosorbent assay, T lymphocyte subsets of peripheral blood were observed by fluorescence activated cell sorting（FACS）. The activitiesof IFN-γ and IL-4 of peripheral blood T lymphocyte members were studied by indirect immunofluorescent antibody method （IFAT）. Results The disappearance of HBeAg occurred in all 29 patients, un-disappearance of HBsAg occurred in 8 of 29 patients. In group of seroconversion（ disappearance of HBsAg）, IL-2, IFN-γ, IL-4 and IL-12 were significantly increased as compared with normal controls （ P 〈 0.05） within 2 weeks and 4-6 weeks. The serum levels of IL-4 within 4-6 weeks was decreased as compared with that of IL-4 within 2 weeks （ P 〈 0.05）. The serum levels of IL-2,IFN - γ,IL-4 and IL-12（ 〉 8 weeks） were decreased as compared with that within 4-6 weeks （ P 〈 0.05）. In group of no seroconversion （without - disappearance of HBsAg）, the variety of IL-4 was different as compared with that of seroconversion. The IL-4 concentrations with in different phases were increased as compared with normal controls（ P 〈 0.05）. No difference were showed in decreased IL-4 levels among different phases. In group of seroconversion, there exists a low ratio of Th1/Th2 within 2 weeks when compared with normal controls（ P 〈 0.05）. However, In Group of no seroconversion, the ratio of Th1/Th2 in different phases was decreased as compared with normal controls（ P 〈 0.05）. At the time of the initial, the serum levels of IFN-γ,when HBV-DNA 〈 10^3, was less than that when HBV-DNA≥ 10^6. Maximal reduction in HBV replication（HBV-DNA 〈 10^3） occurred in 5/8 patients in group of no seroconversion. In group of seroconversion, the CD4^ ＋/CD8^ ＋ ratio at the time of the initial and in 4-6 weeks was decreased as compared with normal controls （ P 〈 0.05）, the CD4 ^＋/CD8^＋ ratio in 4-6 weeks was decreased as compared with that within 2 weeks, and the CD4 ^＋/CDs ^＋ ratio （ 〉 8 weeks）was increased as compared with that in 4-6 weeks （ P 〈 0.05）. The activities of IL-4 in periperal blood T lymphocyte members from patients in group of no seroconversion in different phases were increased as compared with normal controls（ P 〈 0.05）, but no difference among the phases. In group of seroconversion, the activities of IL-4 at the time of the initial and in 4-6 weeks were increased as compared with normal controis（ P 〈 0.05）, the activities of IL-4 （ 4-6 weeks） were decreased as compared with that within 2 weeks, and the activities of IL-4（ 〉 8 weeks） were decreased as compared with that in 4-6 weeks（P 〈 0.05）. Conclusion Our results indicate the corelation between the increased IFN-γ levels and convalescence. Morever, the increased IL-4 levels may also influence convalescence. The regulating the balance of Th1/Th2 may be a new route of preventing chronicity. It is highly important that the CD4 ^＋ T cells and the CD8^＋ T cells bear responsibility for viral clearance, but the imbalance of the CD4 ^＋/CD8^＋ probably resuits in the persistence of HBV infection.