替比夫定对乙肝孕妇T淋巴细胞亚群的影响

The effects of telbivudine on T lymphocyte subsets in pregnancy with hepatitis B virus

目的:分析孕晚期应用替比夫定(Ld T)对乙肝孕妇细胞免疫功能的影响,为降低乙肝高病毒血症孕产妇死亡率提供临床依据。方法:收集2013年3月至12月我院收治的乙肝表面抗原阳性(HBs Ag)阳性、乙肝e抗原(HBe Ag)阳性、HBV DNA≥106IU/ml的59例孕妇,根据孕晚期是否服用Ld T,分为Ld T治疗组和未治疗组。同时收集同期HBs Ag(+)、HBe Ag(-)、HBV DNA<106IU/ml的孕妇30例为低病毒组,HBs Ag(-)的孕妇30例为正常对照组。运用流式细胞术分析Ld T对乙肝孕妇外周血CD3^+T细胞、CD4^+T细胞、CD8^+T细胞及CD4+CD25+Treg细胞(Tregs)的影响。结果:正常组、低病毒组、高病毒未治疗组和高病毒Ld T治疗组的CD3^+T细胞比例无明显差异;与正常组比较,高病毒和低病毒组中CD4^+T细胞比例升高、CD8^+T细胞降低、CD4^+/CD8^+比值进一步升高,Tregs比例显著升高。经Ld T治疗后,T细胞亚群基本处于正常水平。与高病毒未治疗组相比,Ld T治疗组的CD4^+T细胞比例下降,CD8^+T细胞比例也有上升趋势,CD4^+/CD8^+比值显著下降,Tregs比例显著降低。结论:乙肝高病毒血症孕妇体内细胞免疫功能紊乱。Ld T治疗可能解除Tregs对乙肝孕妇机体细胞免疫功能的抑制作用,恢复CD4^+T细胞与CD8^+T细胞之间的平衡状态。Ld T治疗可能通过免疫调节在有效阻断母婴垂直传播的同时,还有可能降低重型肝炎发生率,从而降低孕产妇死亡率。

Objective： To analyze the influence of telbivudine（ Ld T） treatment on cellular immunity in hepatitis B virus（ HBV） seropositive gravidae,which could provide clinical evidence for Ld T therapy for pregnant women with high viremia. Methods： 89 HBV seropositive gravidae were recruited and categorized into different groups according to the titers of serum viral load,low viremia group（ 30 cases,HBV DNA titer 106IU / ml）,high viremia group（ 59 cases,HBV DNA titer ≥106IU / ml）,which was further divided into Ld T-treated-group and non-treated-group in the third trimester basing on patients voluntary choice. 30 seronegative gravidae were as normal controls. Peripheral venous blood were sampled and submitted to analysis of the proportion of CD3~＋T,CD4~＋T,CD8~＋T,CD4~＋CD25~＋Treg cells（ Tregs） by flow cytometry（ FCM） in all the groups. Results： The proportion of CD3~＋T cells among all the groups showed no significant difference. The proportion of CD4~＋T,Tregs and the ratio of CD4~＋/ CD8~＋in high and low viremia group were higher than that in normal group,whereas the proportion of CD8~＋T cells was lower. In Ld T-treated-group,the proportion of T cell subsets returned to normal level,with lower proportion of CD4~＋T cell and Tregs,lower ratio of CD4~＋/ CD8~＋,and higher proportion of CD8~＋T cells,comparing to the non-treated-group. Conclusion： Gravidae with high HBV viremia had abnormal cellular immune function. Ld T treatment may adjust the cellular immune function by reducing the proportion of Tregs and restoring the balance of CD4~＋T and CD8~＋T cells,this might help prevent fulminant virus hepatitis and reduce maternal death.