decreased ratio of treg cells to th17 cells correlates with hbv dna suppression in chronic hepatitis b patients undergoing entecavir treatment减少treg细胞比th17细胞与hbv dna抑制在接受恩替卡韦治疗慢性乙型肝炎患者.pdf

Decreased Ratio of Treg Cells to Th17 Cells Correlates with HBV DNA Suppression in Chronic Hepatitis B Patients Undergoing Entecavir Treatment 1. 1. 2. 1 1 1 Ji-Yuan Zhang , Chun-Hui Song , Feng Shi , Zheng Zhang , Jun-Liang Fu , Fu-Sheng Wang * 1 Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, China, 2 Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Abstract Background: Treatment with nucleotide analogs is known to be effective in inhibiting HBV replication; however, patients with chronic hepatitis B (CHB) often show a wide range of clinical responses to these drugs. Therefore, the identification of an early immunologic marker associated with the clinical outcomes in such cases is critical for the improved clinical management. In our study, we aimed to investigate whether the viral load in CHB patients affected the ratio of the number of regulatory T cells (Tregs) to the number of interleukin-17-producing helper (Th17) cells. Further, we evaluated the clinical implications of the alterations in this ratio. Methodology/Principal Findings: Nine patients seropositive for hepatitis B e antigen received entecavir monotherapy for 12 months and the percentages of Tregs and Th17 cells as well as the HBV-specific IL-17 productions in these patients were longitudinally analyzed. The entecavir-induced suppression of HBV replication was accompanied by a rapid increase in the number of Th17 cells, together with a decrease in Treg cells, which lead to a significant reduction of Treg/Th17 ratios. In addition, peripheral blood mononuclear cells (PBMCs) exhibited a decreased IL-17 production upon stimulation with the HBV core antigen in vitro. Conclusions: The i