Immune correlates of hepatitis B surface antigen spontaneous seroconversion in hepatitis B e antigen negative chronic hepatitis B patients

Abstract

Background Hepatitis B surface antigen (HBsAg) seroconversion in HBeAg −ve chronic hepatitis B (CHB) infection is rare, possibly due to poor antigen processing and impaired humoral response. We investigated the role of dendritic cells (DCs), T follicular helper (TFH) cells and plasma B cells in seroconversion. Methods HBeAg −ve (n=135) CHB patients with raised ALT at baseline were followed up. Patients undergoing HBsAg seroconversion (Gr. I, n=11) were compared with non‐converters with low (Gr. II, n=17, HBV DNA<2000 IU/mL) or high HBV DNA (Gr. III, HBV DNA >2000 IU/mL, n=17). We measured cell phenotypes (TFH, B and DCs), HBV specific T‐cell functionality [using pooled overlapping surface and core peptides], IL21 levels and gene expression analysis by qRT‐PCR. Results Patients in Gr. I compared to Gr. II and III, had higher IL‐21 levels (865 vs 276 vs 111 pg/mL, P=<.0001), TFH (CD4+CXCR5+) cells (12.3 vs 4.67 vs 2.77, P=<.001), inducible T‐cell co‐stimulator (ICOS) expression on TFH cells (20.0 vs 13.0 vs 13.68, P=.01), HBsAg specific IL‐17 (9.40 vs 2.33 vs 2.61, P=<.001) and TNF‐α secreting TFH17 cells (82 vs 1.43 vs 2.33, P=<.001), plasma B (CD19+CD38+) cells (15.0 vs 5.08 vs 5.57, P=<.001), myeloid (17.80 vs 5.39 vs 2.70, P=<.001) and plasmocytoid DCs (2.6 vs 0.43 vs 0.21, P=<.001). Plasma B‐cell frequency (R2=.64, P=.01) and IL‐21 levels (R2=.52, P=.003) correlated with anti‐HBs titres in patients with HBsAg seroconversion. Conclusions Dendritic cell and TFH cell mediated responses regulate humoral responses against HBV and play a major role in HBsAg seroconversion in CHB patients.

Beneficial Effects of Bushen Formula Combined with Enticavir on Chronic Hepatitis B Patients with Suboptimal Response to Enticavir by Regulating B-Cell Differentiation

“…Based on the above results, the immunoregulary roles of BSF on B celluar subtypes were explored. One recent study showed that the frequency of plasma cells correlated with anti-HBs titers in CHB patients with HBsAg seroconversion [33], which suggested that plasma cells contributed to HBsAg seroconversion. It was interesting that the frequency of B-cell was decreased and the frequency of plasma cells was increased after treatment only in T-Group, which maybe the important mechanism of HBsAg decline.…”

‘Status Matters: Relation between MHC levels and Hepatitis B persistence’

“…In our previous study, we reported that CHBV patients have impaired TFh function, which leads to defective antibodies secretion against HBsAg. 5 The study could provide better insight if baseline clinical and immunological profiles of patients as well as reactivation patients group were included in the analyses.…”

Reply

“…Thus, there were limitations in the generalizability of the data. 7 There have been considerable differences in the rates of HBsAg seroclearance between various studies. Seroconversion of HBsAg depends on effective humoral immune responses.…”

“…In CHB patients, impaired T follicular helper cell function has been reported, which leads to defective antibody secretion against HBsAg. 7 The study could provide better insight if baseline and follow-up immunologic profiles of patients were available.…”