Immune correlates of hepatitis B surface antigen spontaneous seroconversion in hepatitis B e antigen negative chronic hepatitis B patients
Background Hepatitis B surface antigen (HB sAg) seroconversion in HB eAg− 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 (DC s), T follicular helper (TFH)
cells and plasma B cells in seroconversion. Methods HB eAg− ve (n= 135) CHB patients
with raised ALT at baseline were followed up. Patients undergoing HB sAg seroconversion
(Gr. I, n= 11) were compared with non‐converters with low (Gr. II, n= 17, HBV DNA< 2000 …
hepatitis B (CHB) infection is rare, possibly due to poor antigen processing and impaired
humoral response. We investigated the role of dendritic cells (DC s), T follicular helper (TFH)
cells and plasma B cells in seroconversion. Methods HB eAg− ve (n= 135) CHB patients
with raised ALT at baseline were followed up. Patients undergoing HB sAg seroconversion
(Gr. I, n= 11) were compared with non‐converters with low (Gr. II, n= 17, HBV DNA< 2000 …
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.
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