慢性乙型肝炎患者抗病毒治疗前后外周血树突状细胞和淋巴细胞亚群的变化及意义

Clinical profiles of circulating dendritic cell phenotype and lymphocyte subsets in patients chronically infected with HBV during lamivudine treatment

目的分析慢性乙型肝炎患者拉米夫定抗病毒治疗前后外周血树突状细胞和淋巴细胞亚群变化。方法对16例拉米夫定抗病毒治疗有效的慢性乙型肝炎患者动态观察48周,在治疗前、后对外周血单核细胞来源的树突状细胞进行体外培养,用流式细胞仪检测DC表面分子及淋巴细胞亚群水平,观察治疗前、后的变化。结果16例患者中,11例治疗持续有效,未发生YMDD变异,5例发生变异。无变异组的慢性乙肝患者,治疗12周时,HLA-DR水平较治疗前降低(P<0·05);治疗48周时,CD80、CD40和CD1a与治疗前比明显提高(P<0·05)而HLA-DR恢复至治疗前水平。变异组患者,治疗12周时,CD83及HLA-DR降低(P<0·05);治疗48周时,HLA-DR仍低于治疗前(P<0·05)。无变异组患者,治疗12周时,CD4+T细胞、CD8+T细胞、NK细胞、CD19+B细胞和CD4+/CD8+T细胞比值均无明显变化;48周时,CD4+T细胞比例增高,NK细胞比例下降(P<0·05)。而变异组患者的淋巴细胞亚群则无显著改变。结论拉米夫定治疗持续有效组,DC表面共刺激分子CD80、CD40可随着HBV被长时间有效抑制而得到部分恢复,治疗过程中有DC表面的HLA-DR暂时降低,而后HLA-DR水平恢复和CD1a明显提高,同时外周血CD4+T细胞比例上升和NK细胞比例下降。而发生YMDD变异组,DC表面HLA-DR呈现持续性降低。

Objective To investigate the subsets in chronic hepatitis B patients treated with changes of circulating dendritic cell （DC） and lymphocytes lamivudine. Methods Sixteen chronic hepatitis B patients treated with lamivudine were included and followed up for 48 weeks in this study. Before and during lamivudine treatment, DC collected from peripheral blood sample was cultured in vitro and surface markers of DC and lymphocytes subsets were detected by flow cytometry simultaneously. Results Of the 16 patients, 11 were consistently HBV DNA negative in serum, and HBV DNA YMDD variants appeared in 5 cases. In the consistent responder group, HLA-DR level of DC decreased transiently in 12 weeks and recovered in 48 weeks （P 〈 0.05 ）. At 48 weeks,CD80 ,CD40 and CD1a were improved compared with baseline level （ P 〈 0.05） . In the YMDD variant greup,CD83 and HLA-DR level of DC decreased at 12 weeks treatment （P 〈 0.05） and HLA-DR was still lower compared with baseline （ P 〈 0.05 ）. In the consistent responder group, no significant changes occurred in lymphocyte subsets number at 12 weeks treatment,but CD4^＋ T cell was improved and NK cell dropped at 48 weeks compared with baseline level （ P 〈 0.05）. In the YMDD variant group lymphocyte subsets had no statistically significant change. Conclusions In the consistent responder group, the expression of surface costimulatory molecules of DC, sueh as CD80 and CD40, was partly recovered after the virus of hepatitis B had been inhibited efficiently,HLA-DR levels of DC decreased transiently at 12 weeks and recovered in 48 weeks, and CD4^＋ T cell improved and NK cell dropped at 48 weeks. In the YMDD variant group, HLA-DR levels of DC were lower consistently during treatment compared with baseline level.