Abstract
A pressing need exists for improved therapeutic options for chronic hepatitis B (CHB). Pegylated-interferon-alpha (Peg-IFN-α) achieves sustained off-treatment responses in many cases because of its direct anti-viral effects and regulation of the immune response. However, non-responsiveness to Peg-IFN-α is frequent, and the mechanism is poorly understood. In this study, we found that the frequency and absolute number of NKp30+ natural killer (NK) cells increased markedly, accompanied by enhanced CD107a and IFN-γ production, during Peg-IFN-α-2b monotherapy or combination therapy with adefovir dipivoxil in patients with CHB, especially in responders. The responders and non-responders differed in the frequency of polyfunctional IFN-γ+ CD107+ NK cells. In addition, the increase in NKp30+ NK cells was negatively correlated with the HBV viral load and plasma HBeAg. Moreover, it was found that IL-15 may contribute to the up-regulation of NKp30 on the NK cells, and this up-regulation was not induced in vitro by Peg-IFN-α-2b alone. However, in the non-responders, these NKp30+ NK cells were dysfunctional because of increased NKG2A expression, which partly explains the inactivation of NKp30+ NK cells and the reduced capacity of these cells to produce antiviral cytokines. These findings may provide a new mechanism to explain the variable efficacy of Peg-IFN-α-2b therapy.
Highlights
Amounts of cytokines, such as IFN-γand TNF-α,and account for 5–10% of all NK cells[12]
We found an increase in CD56bright NK cells during pegylated interferon (Peg-IFN)-α-2b treatment, which is in agreement with the Peg-IFN-α-2a-induced expansion of activated CD56bright NK cells[21]
The combination of Peg-IFN-α-2b with adefovir dipivoxil (ADV) did not result in a higher rate of sustained virological or serological off-treatment response (Supplementary Table 1)
Summary
Amounts of cytokines, such as IFN-γand TNF-α,and account for 5–10% of all NK cells[12]. The current study aims to investigate the immunoregulatory role of Peg-IFN-α- 2b regarding NK cells and viral clearance in HBeAg-positive CHB patients undergoing Peg-IFN-α-2b treatment. The present study evaluated the relationship between NK cells and the response to Peg-IFN-α-2b treatment. A maintenance of the number and recovery of the function of circulating NKp30+ NKG2A− NK cells were found to be closely correlated with a better response to Peg-IFN-α-2b treatment. CHB patients who failed to respond to Peg-IFN-α-2b treatment had increased numbers of NKp30+ NKG2A+ NK cells, indicating that NKG2A was responsible for the dysfunction of the NKp30+ NK cells in the non-responders. The current study explores the important role of NKp30+ NKG2A− NK cells in CHB therapy and extends our understanding of the immunoregulatory role of Peg-IFN-α-2b regarding NK cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
