Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B
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Meng-Ru Zhan1, Xiu-Zhu Gao1, Chang Wang1
1Department of Hepatology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
Insights
Soluble 4-1BB (s4-1BB) levels are significantly elevated in chronic hepatitis B (CHB) patients compared to healthy individuals. Elevated s4-1BB correlates with higher viral load and disease flares, suggesting its potential as a biomarker for CHB progression.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- The costimulatory molecule 4-1BB is crucial in immune responses during chronic viral infections.
- Limited research exists on the role of 4-1BB in chronic hepatitis B (CHB).
Purpose of the Study:
- To investigate the expression levels of 4-1BB in patients with CHB.
- To assess the association of 4-1BB with CHB disease parameters.
Main Methods:
- Plasma levels of soluble 4-1BB (s4-1BB) were measured using ELISA in 64 CHB patients and 37 healthy donors.
- 4-1BB mRNA expression in peripheral blood mononuclear cells was analyzed by real-time quantitative PCR.
- Patients included treatment-naïve and entecavir-treated CHB individuals.
Main Results:
- s4-1BB levels were significantly higher in CHB patients than in healthy adults (P < 0.001).
- Elevated s4-1BB correlated with higher viral load, disease flares, and specific hepatitis B markers (HBsAg, HBV DNA, HBeAg) in treatment-naïve patients.
- No significant difference in s4-1BB levels was observed between treatment-naïve and entecavir-treated CHB patients.
Conclusions:
- Elevated s4-1BB levels indicate a potential association with hepatitis B virus pathogenesis.
- s4-1BB may serve as a promising biomarker for monitoring CHB disease progression.
Background:
Previous 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).
Aim:
To clarify this issue, we report our comprehensive study results on the expression levels of 4-1BB in patients with CHB.
Methods:
From 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.
Results:
The 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.
Conclusion:
These 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.
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