Guojun Shen1, Shuilin Sun2, Jie Huang1, Haohui Deng3, Ying Xu4, Zhanhui Wang4, Xiong Tang1, Xiaodong Gong5. 1. Hepatology Unit, The Third People's Hospital of Jiujiang City, No. 408, Shili Road, Jiujiang, 332000, Jiangxi, China. 2. Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang, Jiangxi, China. 3. Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China. 4. Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. 5. Hepatology Unit, The Third People's Hospital of Jiujiang City, No. 408, Shili Road, Jiujiang, 332000, Jiangxi, China. xdgong1965@126.com.
Abstract
BACKGROUND AND AIMS: T cell-mediated immune injury plays a critical role in the pathogenesis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Given the high short-term mortality and crucial role of T cells in the disease progression, it is necessary to investigate the dynamics of T cell clones during HBV-ACLF. The aim of this study was to longitudinally investigate dynamic changes in the composition and perturbation of T cell receptor β (TCRβ) chain repertoires and to determine whether TCR repertoire characteristics were associated with HBV-ACLF patient outcomes. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected at two time points from 5 HBV-ACLF patients. Global CD4+ and CD8+ T cells were sorted using magnetic beads. TCRβ complementarity-determining region 3 was analyzed by unbiased high-throughput sequencing. RESULTS: During HBV-ACLF, there was a significant decrease in the diversity of T cell repertoires and an increase in proportion of the most 100 abundant clonotypes of CD8 T cells but not CD4. Decreased CD8 repertoire diversity was positively correlated with the reduction of the Model for End-Stage Liver Disease (MELD) score. CONCLUSIONS: There was significant clonal expansion in CD8 but not in CD4 T cell repertoires in HBV-ACLF patients during disease progression. Patients with greater clonal expansions in CD8 T cell repertoires may have better outcomes. CD8 TCRβ repertoire diversity may serve as a potential predictive marker for disease outcome.
BACKGROUND AND AIMS: T cell-mediated immune injury plays a critical role in the pathogenesis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Given the high short-term mortality and crucial role of T cells in the disease progression, it is necessary to investigate the dynamics of T cell clones during HBV-ACLF. The aim of this study was to longitudinally investigate dynamic changes in the composition and perturbation of T cell receptor β (TCRβ) chain repertoires and to determine whether TCR repertoire characteristics were associated with HBV-ACLF patient outcomes. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected at two time points from 5 HBV-ACLF patients. Global CD4+ and CD8+ T cells were sorted using magnetic beads. TCRβ complementarity-determining region 3 was analyzed by unbiased high-throughput sequencing. RESULTS: During HBV-ACLF, there was a significant decrease in the diversity of T cell repertoires and an increase in proportion of the most 100 abundant clonotypes of CD8 T cells but not CD4. Decreased CD8 repertoire diversity was positively correlated with the reduction of the Model for End-Stage Liver Disease (MELD) score. CONCLUSIONS: There was significant clonal expansion in CD8 but not in CD4 T cell repertoires in HBV-ACLF patients during disease progression. Patients with greater clonal expansions in CD8 T cell repertoires may have better outcomes. CD8 TCRβ repertoire diversity may serve as a potential predictive marker for disease outcome.
Authors: Kira Rubtsova; James P Scott-Browne; Frances Crawford; Shaodong Dai; Philippa Marrack; John W Kappler Journal: Proc Natl Acad Sci U S A Date: 2009-04-28 Impact factor: 11.205
Authors: Dmitriy A Bolotin; Stanislav Poslavsky; Igor Mitrophanov; Mikhail Shugay; Ilgar Z Mamedov; Ekaterina V Putintseva; Dmitriy M Chudakov Journal: Nat Methods Date: 2015-05 Impact factor: 28.547