Serum soluble programmed death ligand-1 is correlated with HBsAg level and nucleos(t)ide analogue therapy in chronic hepatitis B
Abstract Background The restoration of immune responses is thought as a complementary approach to the nucleos(t)ide analogue (NUC) therapy of chronic HBV infection. The antiviral immunity is negatively regulated by the programmed cell death-1/programmed death ligand-1 (PD-1/PD-L1) axis. Here, the soluble form of PD-L1 (sPD-L1) that represents the amount of PD-L1 expression cells was used as an indicator to investigate the involvement of this axis in chronic HBV infection, especially in the setting of NUC therapy. Methods A total of 273 adult patients with chronic HBV infection, regardless of the treatment, and 86 healthy controls were consecutively enrolled. Serum sPD-L1 was measured using an ELISA assay. Its correlations with clinical/virological characteristics were analyzed. Results Serum sPD-L1 levels in patients with chronic HBV infection (median 425.2 IQR 245.8-558.6 pg/mL) were significantly higher than those in healthy controls (median 81.69 IQR 54.62-121.1 pg/mL). Among patients at various disease phases, those with immune-tolerant CHB had the lowest sPD-L1 levels (median 205.3 IQR 92.27-340.7 pg/mL). These results indicated that serum sPD-L1 was significantly increased in a manner of two steps from health to infection and from immunotolerance to immunoactivation in chronic HBV infection. Furthermore, the serum sPD-L1 in immune-active CHB was correlated with HBsAg positively, HBV DNA negatively and liver damage marginally. Interestingly, the increased serum sPD-L1 levels were strongly associated with the treatment of NUCs, especially in HBeAg-positive immune-active CHB. Conclusions Serum sPD-L1 might be a meaningful indicator to monitor the immune status and disease progression in chronic HBV infection. The correlations of the increased sPD-L1 with HBsAg and NUC treatment suggest that the activated PD-1/PD-L1 axis may explain the rarity of HBsAg seroconversion of NUC therapy and the clinically available checkpoint inhibitors may serve as partners for NUCs to improve their anti-HBV efficacy in the future.
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Preprint| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
ResearchSquare.com - (2020) vom: 03. Sept. Zur Gesamtaufnahme - year:2020 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ke, Ruo Man [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-17628/v1 |
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| PPN (Katalog-ID): |
XRA034108653 |
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| 245 | 1 | 0 | |a Serum soluble programmed death ligand-1 is correlated with HBsAg level and nucleos(t)ide analogue therapy in chronic hepatitis B |
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| 520 | |a Abstract Background The restoration of immune responses is thought as a complementary approach to the nucleos(t)ide analogue (NUC) therapy of chronic HBV infection. The antiviral immunity is negatively regulated by the programmed cell death-1/programmed death ligand-1 (PD-1/PD-L1) axis. Here, the soluble form of PD-L1 (sPD-L1) that represents the amount of PD-L1 expression cells was used as an indicator to investigate the involvement of this axis in chronic HBV infection, especially in the setting of NUC therapy. Methods A total of 273 adult patients with chronic HBV infection, regardless of the treatment, and 86 healthy controls were consecutively enrolled. Serum sPD-L1 was measured using an ELISA assay. Its correlations with clinical/virological characteristics were analyzed. Results Serum sPD-L1 levels in patients with chronic HBV infection (median 425.2 IQR 245.8-558.6 pg/mL) were significantly higher than those in healthy controls (median 81.69 IQR 54.62-121.1 pg/mL). Among patients at various disease phases, those with immune-tolerant CHB had the lowest sPD-L1 levels (median 205.3 IQR 92.27-340.7 pg/mL). These results indicated that serum sPD-L1 was significantly increased in a manner of two steps from health to infection and from immunotolerance to immunoactivation in chronic HBV infection. Furthermore, the serum sPD-L1 in immune-active CHB was correlated with HBsAg positively, HBV DNA negatively and liver damage marginally. Interestingly, the increased serum sPD-L1 levels were strongly associated with the treatment of NUCs, especially in HBeAg-positive immune-active CHB. Conclusions Serum sPD-L1 might be a meaningful indicator to monitor the immune status and disease progression in chronic HBV infection. The correlations of the increased sPD-L1 with HBsAg and NUC treatment suggest that the activated PD-1/PD-L1 axis may explain the rarity of HBsAg seroconversion of NUC therapy and the clinically available checkpoint inhibitors may serve as partners for NUCs to improve their anti-HBV efficacy in the future | ||
| 700 | 1 | |a Ouyang, Li Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Wen Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ming Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Xiao Mou |e verfasserin |4 aut | |
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