Relationship between interferon-alpha efficacy and the expression of programmed death 1 and T-cell immunoglobulin and mucin domain-containing molecule 3 on peripheral blood CD8+ T cells in patients with chronic hepatitis B

Abstract

Objective To investigate the association of interferon-alpha (IFN-α) antiviral efficacy and the expression of programmed death 1 (PD-1) and T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim3) on peripheral blood CD8+T cells in patients with chronic hepatitis B (CHB). Methods Total of 72 CHB patients with HBeAg positive were collected, and their anti-coagulation peripheral venous blood were collected from each patient at the beginning and the end of 12 months of IFN-α therapy. Thirty cases of healthy individuals were enrolled as controls. PD-1 and Tim3 on CD8+T cells were detected by flow cytometry. Results Before IFN-α treatment, the median percentage of PD-1 and Tim3 on peripheral blood CD8+T cells was 35.5% and 4.8% in CHB, respectively, and both were higher than the corresponding index in healthy control group (29.3% and 3.6%), with significant differences (U = 805.0,P = 0.043;U = 741.5,P= 0.013). At the end of 12 months of IFN-α therapy, the median percentage of PD-1 and Tim3 on CD8+T cells was 32.7% and 4.1% in CHB patients, respectively, and significantly decreased than those before treatment (Z= 3.305,P= 0.001;Z= 2.065,P= 0.039). The median percentage of the two molecule expression was significantly lower in patients who achieved HBeAg seroconversion than those of patients without HBeAg seroconversion, with significant differences (U= 209.0,P < 0.001;U= 302.0,P <0.001). The two median percentages were without significant difference between ALT normalization and abnormalization groups (U = 229.5,P = 0.635;U= 209.5,P = 0.405). The median percentage of PD-1 on CD8+T cells was significantly lower in patients with HBV DNA undetectable than those with detectable HBV DNA (U= 371.5,P = 0.011), which was not significantly different between the two groups of patients (U = 558.0,P = 0.727). Conclusions A higher expression of PD-1 and Tim3 on peripheral blood CD8+T cells was presented in CHB patients, which could be downregulated by IFN-α therapy, and the decreased expression was associated with the efficacy of IFN-α treatment. Key words: Chronic hepatitis B; Interferon alpha; Peripheral blood CD8+T lymphocyte; Programmed death 1; T-cell immunoglobulin and mucin domain-containing molecule 3