Contribution of NK cells to HBsAg seroconversion in inactive HBsAg carriers following pegylated IFN therapy

Abstract

Our recent study showed a high rate of HBsAg seroconversion in inactive HBsAg carriers (IHCs) treated with pegylated IFN (PEG-IFN). To understand the immune-mediated component of the HBsAg seroconversion better, this study investigated the role of NK cells. A total of 44 IHCs were given 48 wk of PEG-IFN. Fifteen cases achieved HBsAg seroconversion (R group), whereas 29 failed (NR group). The proportion and activity (CD107α and IFN-γ production) of NK cells were measured before and during treatment. We found that the proportion of NK cells in the R group was higher than in the NR group at baseline and during PEG-IFN treatment, even when patients were matched for age, sex and treatment period. IFN- γ secretion and CD107α expression from NK cells in cases who achieved HBsAg seroconversion were significantly higher than patients matched for age, sex, HBsAg and treatment period in the NR group at baseline and during PEG-IFN treatment. We also found that in HBsAg seroconversion cases, NK cells activity increased after PEG-IFN treatment, especially before HBsAg seroconversion. These effects were not found in non-responders. In conclusion, we demonstrated that the increase of NK cells accompanied by enhanced activity during PEG-IFN treatment favoured HBsAg seroconversion for IHC, and that NK cells may play a role in HBV seroconversion.

Functional molecular expression of nature killer cells correlated to HBsAg clearance in HBeAg-positive chronic hepatitis B patients during PEG-IFN α-2a therapy

“…NKp46, as the activating receptor of NK cells, may regulate the activity of NK cells in the suppression of HBV replication and HBV-related liver injury, meanwhile, it is crucial for the activation of NK cells in chronic HBV infection (42). Our resluts showed that after therapy, the frequency of NKp46 high NK cells and surface reporters IFNAR2 and NKp46 expression on NK cells in patients with HBsAg loss significantly increased, which was consist with some studies suggesting that in patient with CHB, the expression of IFNAR2 and NKp46 on the surface of NK cells elevated after PEG-IFN therapy (32,33), NKp46 high NK cells may be closely correlated to HBV clearance, and up-regulated expression of NKp46 high is beneficial to the clearance of HBV.…”

“…In a variety of treatment methods for CHB, PEG-IFN has antiviral role and immunomodulatory effect. Previous studies have shown that PEG-IFN therapy can enhance function of NK cells and facilitate virus clearance ( 13 , 31 – 33 ). NK cells were the important part of innate immunity.…”

“…After IFN treatment, remarkable increase in expansion and activation of CD56 bright NK cells, IFN-γ production, and augmentation of NK cell activating receptors (NKp46 and NKp30) expression are observed ( 30 , 31 ). After PEG-IFN treatment, the recovery of CD56 bright NK cells function and expansion of percentages of NKp46 + and CD56 bright NK cells were revealed in inactive HBsAg carriers and CHB patients with NAs therapy ( 32 , 33 ). The percentage and functional molecular expression of NK cells correlated to HBsAg clearance in treatment-naive HBeAg-positive CHB patients during PEG-IFN α-2a therapy are relatively rare.…”

Hepatitis B functional cure and immune response

“…In addition, NK cell activity had an increase in patients with HBsAg seroconversion group, especially before the seroconversion of HBsAg, which were not seen in patients without HBsAg seroconversion. In summary, PegIFNα induced NK cells to increase with enhanced activity, which is conducive to the HBsAg seroconversion of IHCs ( 77 ).…”