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替诺福韦加聚乙二醇干扰素连续治疗
提高树突状细胞和CD8 + T细胞的功能显着降低PD-1
相比替诺福韦单药治疗在
CONTROL ID: 1424569
PRESENTATION TYPE: Oral or Poster
CURRENT CATEGORY: Hepatitis B
CURRENT DESCRIPTORS: I02. Treatment and Clinical Trials
TITLE: Sequential Therapy with Tenofovir plus Peg Interferon Improves Dendritic Cell and CD8 T cell Functions by Significant Reduction in PD-1 Compared with Tenofovir Montherapy in Chronic Hepatitis B (CHB) Patients
AUTHORS (FIRST NAME, LAST NAME): Nirupma Trehanpati1, Arshi Khanam1, Tarandeep Singh1, Ankit Bhardwaj1, Ankur Jindal2, Syed Hissar1, Shiv K. Sarin1, 2
Institutional Author(s):
INSTITUTIONS (ALL): 1. Research, Institute of liver and biliary sciences, New Delhi, India.
2. Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
ABSTRACT BODY: Background: Dendritic cells (DCs) are antigen presenting cells, responsible for initiating antiviral immunity and induction of T cell mediated response. Functional defects have been observed in DCs of CHB patients. Reduction in HBV viral load alone or followed by addition of interferon (sequential therapy) to enhance immune modulation are logical strategies to achieve rapid and effective HBV clearance. Aim: To investigate relative functional restoration of DCs in HBeAg+ve CHB patients, receiving Tenofovir mono-therapy and tenofovir plus pegylated interferon (Peg-IFN) sequential therapy. Methods: Sixty histologically proven CHB patients were recruited and randomly divided into two groups; Group1(n=36) received Tenofovir 300mg/day monotherapy for the 48 weeks and Group 2 (n=24) received Tenofovir alone till week 12, followed by Tenofovir+ Peg-IFN till week 36 and subsequently tenofovir till week 48. PBMCs were isolated from patients at baseline and 24 week. Frequency of circulating myeloid (mDCs) and plasmacytoid dendritic cells (pDCs), costimulatory molecules CD80, CD83, toll like receptor TLR7,TLR 9 and CCR7 was analysed on DCs by flow cytometery. In vitro generated immature DCs were stimulated with resiquimod (TLR7/8 agonist) and CPG oligonucleotide (TLR9 agonist) and IFN-α and TN-α level was measured. Phagocytic assay was performed to analyse antigen uptake by DCs. Results: More than 2 Log HBV DNA reductions was observed in both groups at week 24. No difference in frequencies of mDCs and pDCs was observed at baseline and 24 week. Sequential therapy significantly increased the frequency of CD8 T cells (p=0.02), memory T cells (CD8+CD127+) (p=0.03) and decreased programmed death-1(PD1) expression on CD8 T cells (p=0.03) compared with tenofovir monotherapy in CHB patients. CD80 and 83 expression was increased in both groups.CCR7 expression on mDCs and HLA-DR expression required for antigen presentation was upregulated in both groups at 24 weeks compared to baseline (p<0.05). Significant (<0.05) increase in TLR9 but not TLR7 expression on mDCs was observed in group 2. Phagocytic activity of DCs was enhanced from baseline in group 1 (9.5%vs61.4% p= 0.05) and 2 (8.9%vs.21.6% p= 0.08). IFN-α and TNF-α production by mDCs and pDCs improved at week 24 in both groups. Conclusion: Improved functionality of dendritic cells with tenofovir monotherapy as well as sequential therapy is related to reduction in HBV DNA levels. Sequential therapy using PEG IFN was significantly superior in restoring CD8 T cell mediated immunity and TLR9 functions on DCs. Our results support the role of immune restoration and modulation in HBV clearance using sequential therapy.
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