肝移植受者外周血CTL及Th1细胞占比变化与乙肝疫苗接种成功的相关性

Correlation between CTL and Th1 cell proportion in peripheral blood of liver transplantation recipients and the success of hepatitis B vaccination

目的探讨肝移植受者外周血细胞毒性T淋巴细胞(CTL)及Th1细胞占比变化与乙肝疫苗接种成功的相关性。方法以在解放军总医院第三医学中心肝脏移植科长期随诊的乙肝相关性肝病肝移植受者为研究对象,将受试者随机分为两组进行前瞻性研究:快速组在第0、1、2、3个月各接种1剂40 μg乙肝疫苗,第4、5、6个月各接种20 μg;快速加强组在第0、1、2、3个月各接种1剂40 μg乙肝疫苗,第4、5、6个月各接种60 μg。比较分析两组接种成功率、接种前后外周血乙肝表面抗体(抗-HBs)滴度及CTL细胞占CD8^+T细胞比例、Th1细胞占CD4^+T细胞比例变化,对CTL细胞及Th1细胞变化幅度与抗-HBs变化幅度进行相关分析。观察疫苗接种的安全性。结果快速加强组接种成功率、抗-HBs增幅、CTL细胞占比增幅及Th1细胞占比增幅均大于快速组,差异有统计学意义,分别为38.3%(23/60)比21.7%(13/60)(P=0.046)、91.3(72.5,124.2)比22.1(12.4,31.6)(P=0.001)、1.4(0.8,1.9)比0.4(0.2,1.4)(P=0.001)和7.4±2.6比5.6±3.7(P=0.001)。成功组CTL细胞占比增幅和Th1细胞占比增幅均大于非成功组,差异有统计学意义,分别为1.9(1.4,2.5)比0.1(0.0,1.1)(P=0.024)和9.6±3.1比2.4±2.0(P<0.001)。全组资料抗-HBs增幅(105.5±37.1)与CTL细胞占比增幅1(0,3)无相关性(P=0.099)而与Th1细胞占比增幅7(2,11)呈正相关(P<0.001)。研究期间未发生排斥反应,安全性指标无特殊异常变化。结论合理增加疫苗剂量可上调Th1细胞表达,进而促进抗-HBs生成。

Objective To investigate the correlation between the proportion of CTL and Th1 cells in peripheral blood of liver transplant recipients and the success of hepatitis B vaccination. Methods The subjects of this study were liver transplantation recipients with chronic HBV-related liver diseases in Organ transplantation institute of the third medical center of PLA general hospital. Subjects were randomly divided into two groups for prospective study. In the rapid group, one dose of 40 μg hepatitis B vaccine was administered at 0, 1, 2and 3 months, and one dose of 20 μg hepatitis B vaccine was administered at 4, 5 and 6 months. In the rapid-enhanced group, one dose of 40 μg hepatitis B vaccine was administered at 0, 1, 2 and 3 months, and one dose of 60 μg hepatitis B vaccine was administered at 4, 5 and 6months. Compare and analyze the success rate of inoculation, the titer of hepatitis B surface antibody (anti-HBs), the proportion of CTL cells in CD8^+T cells and Th1 cells in CD4^+T cells. Correlation analysis was performed for CTL and Th1 cells and anti-HBs, Observe the safety of vaccination. Results The inoculation success rate, anti-HBs growth rate, CTL cell percentage increase and Th1 cell percentage increase in the rapid enhancement group were all higher than those in the rapid enhancement group, and the differences were statistically significant, they were 38.3%(23/60) vs 21.7%(13/60)(P=0.046), 91.3(72.5,124.2) vs 22.1(12.4, 31.6)(P=0.001), 1.4(0.8,1.9) vs 0.4(0.2,1.4)(P=0.001) and 7.4±2.6 vs 5.6±3.7 (P=0.001) respectively. The percentage increase of CTL cells and Th1 cells in the successful group was greater than that in the non-successful group, and the difference was statistically significant. They were 1.9(1.4,2.5) vs 0.1(0.0,1.1)(P=0.024) and 9.6±3.1 vs 2.4±2.0 (P<0.001). There was no significant correlation between anti-HBs increase (105.5±37.1) and CTL increase 1(0,3)(P=0.099), while there was significant positive correlation with Th1 increase 7(2,11)(P<0.001). No rejection reaction occurred during the study period, and there was no special abnormal change in the safety index. Conclusion Reasonable increase of vaccine dose can up-regulate Th1 cell expression and promote the generation of anti-HBs .