Background: The negative signal provided by some co-inhibitory factors such as programmed cell death-1 (PD-1) has been associated with chronic hepatitis B (CHB) infection induced-T cell exhaustion, although the correlation of CpG methylation of the Pdcd1 gene with PD-1 expression and medical laboratory indicators in CHB infection has not yet been elucidated.
Methods: Blood samples from 20 CHB infection patients and 20 spontaneous clearance (SC) patients were collected. Percentages of PD-1-positive CD8+ T cells were analyzed by flow cytometry. The percentage of CpG methylation at the Pdcd1 locus was analyzed by bisulfite sequencing. Student's t test, Pearson and Spearman's correlation, and Mann-Whitney tests were used in the statistical analysis.
Results: Percentages of PD-1-positive CD8+ T cells in peripheral blood T cells were significantly higher in CHB patients than in the SC group (p < 0.001). The methylation level of Pdcd1 was significantly lower in CHB patients (p < 0.001) and the methylation level of Pdcd1 was negatively correlated with PD-1 expression level in CD8+ T cells (p < 0.001) and hepatitis-B surface antigen (HBsAg) (p < 0.001).
Conclusions: The results of the present study suggest that Pdcd1 methylation is correlated with PD-1 expression on CD8+ T cells and correlated with HBsAg and alanine aminotransferase. The results may provide new ideas regarding anti-PD-1 inhibitors, and epigenetic regulators such as demethylation inhibitors could represent more successful therapeutic strategies in hepatitis B infection patients.
Keywords: Pdcd1; chronic hepatitis B infection; methylation; programmed death-1.
© 2019 John Wiley & Sons, Ltd.