干扰素α-2b治疗HBeAg阳性慢性乙型肝炎患者CD4^+/CD8^+T细胞活化分子CD69和HLA-DR的表达

Study on the expression of HLA-DR/CD69 on CD4^+/CD8^+T cells in the treatment of HBeAg-positive chronic hepatitis B with interferon alfa-2b

目的观察HBeAg阳性慢性乙型肝炎患者干扰素α-2b治疗前、中、后期CD4+/CD8+T细胞的活性与疗效的相关性。方法 32例患者隔日1次干扰素5 MU肌注,共24周。抽取干扰素α-2b治疗前,治疗1、4、12、24周的外周静脉血,密度梯度离心法分离获得外周血单个核细胞(PBMC),流式细胞仪检测CD4+/CD8+T细胞比例及CD4+/CD8+T细胞表面CD69、HLA-DR的表达。结果干扰素α-2b治疗结束,HBV DNA含量转阴者12例(37%),其中HBeAg、抗-HBe血清转换5例(16%);12例治疗无效(37%)及8例HBV DNA抑制(25%)。HBV DNA转阴者治疗前,治疗1、4周时CD69、HLA-DR表达率较治疗无效及HBV DNA抑制者高,差异有统计学意义(P<0.05)。HBV DNA转阴者治疗后1周时,CD69、HLA-DR表达率最高;4周时CD4+/CD8+T细胞的CD69、HLA-DR表达率较前下降,但仍保持较高表达率;12周时CD69、HLA-DR表达率较前更下降,与治疗无效及HBV DNA抑制者相比差异无统计学意义(P﹥0.05);24周时CD69、HLA-DR表达率最低,与治疗无效及HBV DNA抑制者比较差异有统计学意义(P<0.05)。结论 HBeAg阳性慢性乙型肝炎患者CD4+/CD8+T细胞活化分子CD69、HLA-DR的表达,对干扰素α-2b的疗效有预测作用。

Objective To study the efficacy prediction and the activation of CD4 ＋/CD8 ＋ T cells in the treatment of HBeAg - positive chronic hepatitis B with interferon alfa - 2b. Methods 32 patients were given interferon alfa - 2b 5 MU every other day for 24 weeks. PBMC were isolated from fresh peripheral blood of chronic severe hepatitis B patients by Ficoil - Hypaque density gradient centrifugation and cul- tured with plastic - adherence method. FACS was used to analyze the expression of the CD4 ＋/CD8 ＋ T cells surface markers, including hu- man leukocyte antigen - DR （ HLA - DR） and CD69. Results At the end of treatment, HBV - DNA levels loss rates were 37% （ 12 ca- ses）, including HBeAg seroconversion in 5 cases（ 16% ）. In 8 cases（25% ） HBV - DNA levels were decreased and 12 cases （37%） were ineffective. Although interferon alfa -2b had no effects on the ratio of CIM ＋/CD8 ＋ T ceils in chronic severe hepatitis B patients, the ex- pression of CD4＋/CD8 ＋ T ceils activators, such as CD69 and HLA - DR were upregulated , especially in negative HBV - DNA cases. At 1, 4,12,24 weeks, there was significant difference （ P 〈 0.05 ）. Compared with the decreased and ineffective cases, CD69/HLA - DR expression rates in negative HBV - DNA cases were the lowest at 24 weeks （ P 〈 0.05 ）. Conclusion Interferon alfa - 2b can Up - regulate the expression of CD69/HLA - DR on CD4 ＋/CD8 ＋ T cells. The activation of CD4 ＋/CD8 ＋ T cells levels can predict the efficacy in the treatment of HBeAg - positive chronic hepatitis B with interferon alfa - 2b.