Seroconversion Through IL-21 in Patients with Chronic HBV Infection

Given the clinical significance of hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B virus (HBV) infection, it is critical to elucidate the mechanisms regulating this process. In the present study, we found that the frequency of circulating CXCR5 + CD4 + T cells was higher in patients who had achieved HBeAg seroconversion in both cross-sectional (P<0.001) and longitudinal (P=0.009) studies. These cells were able to produce significantly higher level of intracellular IL-21 following stimulation with HBV peptides in patients with Telbivudine-induced HBeAg seroconversion (P=0.007). Furthermore, the sorted CXCR5 + CD4 + T cells from the HBeAg seroconverters boosted a higher frequency of anti-HBesecreting B cells in co-culture assay (P=0.011). Of note, the increase in frequency of anti-HBe-secreting B cells was abrogated by soluble rIL21R-Fc (P=0.027), whereas exogenous rIL-21 enhanced this effect (P=0.043). Additionally, circulating CXCR5 + CD4 + T cells shared similar phenotypic markers to and was positively correlated in frequency with splenic follicular T helper cells. Conclusions: Circulating CXCR5 + CD4 + T cells, by producing IL-21, may have a significant role in facilitating HBeAg seroconversion in patients with chronic HBV infection. Page 3 of 35 Hepatology Hepatology