JAK-STAT信号通路介导BLIMP1-BCL6轴激活在慢性HBV感染临床转归中的作用研究

乙型肝炎病毒感染可表现为急性肝炎、慢性肝炎、重型肝炎到肝硬化、肝细胞癌等多种不同的临床表型。导致慢性HBV感染不同结局最重要的原因是宿主免疫遗传因素，其影响慢性HBV感染和疾病进程的诸多阶段，对慢性HBV感染后疾病的变化发展发挥着关键作用。PRDM1/BLIMP1和BCL6是一对相互抑制的转录因子，受JAK-STAT信号通路调控，不仅参与调节T细胞不同亚群的分化，而且调节Tfh细胞发育和活化从而影响慢性HBV感染的临床结局。本研究拟采用高通量测序技术构建JAK-STAT信号通路和BLIMP1-BCL6的突变谱，分别从常见突变及罕见变异两个角度分析其与HBV感染后临床结局和调节Tfh细胞表型和功能的作用以及疾病预后相关指标的关联性，为慢性HBV感染疾病进展的判断和预后预测以及未来基于个体遗传背景的免疫遗传学治疗方法的设计提供新的线索和依据。

Infection with hepatitis B virus (HBV) is associated with a variety of clinical diseases including acute and chronic hepatitis, severe hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). The host immunological and genetic factors are regarded as critical determinants of the outcomes of HBV infection in view of the noncytopathic effect of HBV replication in hepatocytes. PRDM1/BLIMP1 and BCL6 regulated by JAK-STAT signaling pathway are a pair of mutually inhibiting transcription factors. They not only regulate the differentiation of different subsets of T cells, but also regulate the development and activation of Tfh cells, thus affecting the clinical outcomes of chronic HBV infection. The purpose of this study is to construct JAK-STAT signaling pathway and mutation spectrum of BLIMP1-BCL6 by high-throughput sequencing technology and analysis the relationship among the common mutations with rare mutations in the different clinical outcomes after HBV infection, the role of Tfh cell phenotype and function regulation, and prognostic indicators of chronic HBV infection, which provided new clues and basis for judging the progress of chronic HBV infection and predicting the prognosis, as well as the design of immunogenetic therapy based on individual genetic background in the future.