Role Of Tfh Cell-mediated Humoral Immune Response In The Process Of HBeAg Seroconversion In CHB Patients Receiving Peginterferon-Αlpha Therapy

Background: Hepatitis B e antigen(HBeAg) seroconversion constitutes a significant milestone in the treatment of HBeAg-positive patients with chronic hepatitis B(CHB), but studies have yet to identify the specific humoral immune mechanisms behind the process or any accurate markers that can determine the virus-host immune status and, thereby, predict the degree of HBeAg seroconversion achievable.Methods: The frequencies and phenotypes(i.e., ICOS, PD-1, CD40 L, IL-21 R, ICOSL, PD-L1, and CD40 expression) of circulating Tfh cells and CD19+ B cell subtypes were measured by using of flow cytometry in HBeAg-positive CHB patients undergoing PEG-IFN-α treatment. The levels of serum HBV DNA, HBV-related HBsAg, anti-HBs, HBeAg, anti-HBe, ALT and AST were determined. Univariate and multivariate logistic regressions were applied to assess the independent predictors of PEG-IFN-α-induced HBeAg seroconversion.Results: In the present longitudinal study, higher frequencies of circulating CXCR5+CD4+ T cells and CD19+CD38+ B cells were found in peginterferon-α treated HBeAg-positive CHB patients in whom HBeAg seroconversion had been achieved. Both cell types peaked at 24 weeks for the HBeAg seroconversion group, while showing only a slight variation in the HBeAg non-seroconversion group. Moreover, the data showed a negative correlation between the concentration of HBeAg and the frequency of CXCR5+CD4+ T cells at 24 weeks and the frequency of CXCR5+CD4+ T cells at 24 weeks had a positive correlation with the frequency of CD19+CD38+ B cells at 24 weeks. What’s more, the frequency of PD-1+CXCR5+CD4+ T cells presented a general downward trend in the HBeAg seroconversion group from baseline to 24 weeks, while this frequency was found to increase in the HBeAg non-seroconversion group. And the frequency of PD-L1+CD19+CD38+ B cells demonstrated a larger decline in the HBeAg seroconversion group, comparatively. However, no significant trends were found in both group. In addition, circulating CXCR5+CD4+ T cells and hepatitis B surface antigens(HBsAg) were assessed at 24 weeks and 12 weeks, respectively, and the use of their ratio was explored in terms of its ability to predict HBeAg seroconversion.Conclusion: Dysfunction of the humoral immune response mediated by CXCR5+CD4+ T cells is associated with the failure of HBeAg seroconversion. The CXCR5+CD4+ T cells/HBsAg ratio is an ideal marker for predicting HBeAg seroconversion in CHB patients.