目的探讨γ干扰素(interferon-γ,IFN-γ)基因+874位点和白介素-2(interleukin-2,IL-2)基因-330位点的基因多态性在慢性乙型肝炎病毒(Hepatitis B virus,HBV)和/或丙型肝炎病毒(Hepatitis C virus,HCV)感染者临床转归中的交互作用。方法...目的探讨γ干扰素(interferon-γ,IFN-γ)基因+874位点和白介素-2(interleukin-2,IL-2)基因-330位点的基因多态性在慢性乙型肝炎病毒(Hepatitis B virus,HBV)和/或丙型肝炎病毒(Hepatitis C virus,HCV)感染者临床转归中的交互作用。方法对20世纪80年代末河北某农村单采血浆献血员中的HBV/HCV感染者进行分析,采用多因子降维法(multifactor dimensionality reduction method,MDR)分析IFN-γ+874和IL-2-330基因多态性在慢性HBV/HCV感染者临床转归中有无交互作用,风险评价用比值比(odds ratio,OR)和95%置信区间(confidence interval,95%CI)表示,交互作用评价指标主要为超额相对危险度(relative excess risk of interaction,RERI)、95%CI、交互作用指数(synergy index,SI)、交互作用归因比(attributable proportion of interaction,API)。结果①辅助性T细胞(helper T cell,Th cell)Th1类主要细胞因子IFN-γ+874、IL-2-330位点,对HBV/HCV感染者的临床不良转归有交互作用(P=0.001),检验准确度为0.6313,交叉验证一致性为10/10;②IFN-γ+874 AA和IL-2-330 TT基因型共存时,HBV/HCV感染者不良临床转归的OR值分别为10.13(2.25~45.68,轻型肝炎)、10.56(2.09~53.26,中重型肝炎)和13.57(2.18~84.37,肝硬化)差异有统计学意义(χ^(2)=19.84,P=0.02),分别是IFN-γ+874 AA基因型单独暴露时的6.80、4.06和8.13倍,是IL-2-330 TT基因型单独暴露时的8.37、8.06和6.56倍;③IFN-γ+874 AA和IL-2-330 TT基因型共存时,HBV/HCV感染者进展为轻型、中重型肝炎和肝硬化的交互作用指数(SI)分别为13.04、5.01和7.22;RERI分别为8.43(2.61~27.23)、7.65(2.50~23.42)和10.83(2.53~46.32);API分别为83.22%、72.44%和79.81%。结论慢性HBV/HCV感染者Th1类主要细胞因子IFN-γ+874 AA和IL-2-330 TT基因型共存时对HBV/HCV感染者的不良临床转归表现为协同交互作用。展开更多
To characterize acute-phase hepatitis B virus (HBV)-specific T cell responses associated with self-limited and persistent HBV infections, we compared a patient with acute HBV/HCV coinfection, who was able to control H...To characterize acute-phase hepatitis B virus (HBV)-specific T cell responses associated with self-limited and persistent HBV infections, we compared a patient with acute HBV/HCV coinfection, who was able to control HCV but developed chronic hepatitis B, with patients who resolved acute HBV infection spontaneously. Acute-phase CD4 responses were efficient in self-limited infections but undetectable in the coinfected patient with HBV persistence. CD8 responses were multispecific irrespective of the outcome of infection, but the CD8 repertoire associated with HBV persistence lacked the most dominant specificities detectable in self-limited infections. In conclusion, insufficient CD4 help and defective CD8 repertoire may play a role at the early stages of infection in influencing HBV persistence.展开更多
基金The National Nature Science Foundation of China(1137136911101323)+2 种基金the Natural Science Basic Research Plan in Shaanxi Province(2013JM1002)the Foundation of Shaanxi Provincial Education Department(12JK0855)the Scientific Research Foundation of Xi’an Polytechnic University(BS1208)
文摘To characterize acute-phase hepatitis B virus (HBV)-specific T cell responses associated with self-limited and persistent HBV infections, we compared a patient with acute HBV/HCV coinfection, who was able to control HCV but developed chronic hepatitis B, with patients who resolved acute HBV infection spontaneously. Acute-phase CD4 responses were efficient in self-limited infections but undetectable in the coinfected patient with HBV persistence. CD8 responses were multispecific irrespective of the outcome of infection, but the CD8 repertoire associated with HBV persistence lacked the most dominant specificities detectable in self-limited infections. In conclusion, insufficient CD4 help and defective CD8 repertoire may play a role at the early stages of infection in influencing HBV persistence.
