Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B

BACKGROUNDPrevious studies have suggested that the costimulatory molecule 4-1BB plays pivotal roles in regulating immunity during chronic viral infection. However, up to now, there are few studies about 4-1BB in chronic hepatitis B (CHB).AIMTo clarify this issue, we report our comprehensive study results on the expression levels of 4-1BB in patients with CHB.METHODSFrom September 2018 to June 2019, a total of 64 patients with CHB were recruited from the Department of Hepatology, The First Hospital of Jilin University. Peripheral blood samples were collected from 52 treatment-naïve and 12 entecavir-treated patients with CHB as well as 37 healthy donors (including 24 healthy adults and 13 healthy children). The levels of soluble 4-1BB (s4-1BB) in plasma were measured by ELISA. 4-1BB mRNA expression in peripheral blood mononuclear cells was detected by real-time quantitative PCR.RESULTSThe s4-1BB levels in the plasma of patients with CHB were significantly higher than those in healthy adults (94.390 ± 7.393 ng/mL vs 8.875 ± 0.914 ng/mL, P < 0.001). In addition, the s4-1BB level in plasma was significantly increased in patients with a higher viral load and a disease flare up. However, there were no significant differences between treatment-naïve and entecavir-treated patients. Interestingly, among treatment-naïve patients with CHB, the levels of s4-1BB in plasma had a significant positive correlation with hepatitis B surface antigen, hepatitis B virus DNA, hepatitis B e antigen, and triglyceride levels (r = 0.748, P < 0.001; r = 0.406, P = 0.004; r = 0.356, P = 0.019 and r = -0.469, P = 0.007, respectively). The 4-1BB mRNA expression was higher in the peripheral blood mononuclear cells of patients with CHB than in the peripheral blood mononuclear cells of healthy adults, but the difference was not statistically significant.CONCLUSIONThese results suggest that the levels of s4-1BB may be associated with pathogenesis of hepatitis B virus and therefore may be a promising biomarker for disease progression.