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.

• Authors: Ashish Kumar Vyas, Barjesh Chander Sharma, Shiv Kumar Sarin, Nirupma Trehanpati
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 38 Issue 1 Pg. 38-49 (01 2018) ISSN: 1478-3231 [Electronic] United States
• PMID: 28500636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• DNA, Viral
• Hepatitis B Antibodies
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens
• ICOS protein, human
• Inducible T-Cell Co-Stimulator Protein
• Interleukins
• TLR7 protein, human
• Toll-Like Receptor 7
• interleukin-21

Topics

• B-Lymphocytes (immunology, virology)
• Biomarkers (blood)
• Cells, Cultured
• DNA, Viral (blood, genetics)
• Dendritic Cells (immunology, virology)
• Hepatitis B Antibodies (blood, immunology)
• Hepatitis B Surface Antigens (immunology)
• Hepatitis B e Antigens (immunology)
• Hepatitis B virus (genetics, immunology)
• Hepatitis B, Chronic (blood, diagnosis, immunology, virology)
• Host-Pathogen Interactions
• Humans
• Immunity, Humoral
• Inducible T-Cell Co-Stimulator Protein (immunology)
• Interleukins (immunology)
• Seroconversion
• T-Lymphocytes, Helper-Inducer (immunology, virology)
• Toll-Like Receptor 7 (immunology)
• Viral Load