Differential Methylation Patterns Predict HBsAg Seroconversion in Hepatitis B Virus Reactivation Patients.

Area of Science:

• Immunology
• Epigenetics
• Virology

Background:

• Hepatitis B virus (HBV) infection is known to modulate the immune system's epigenetic landscape.
• Understanding these epigenetic changes is crucial for developing effective therapeutic strategies.

Purpose of the Study:

• To investigate the immune epigenetic landscape in individuals who have cleared HBV (seroconverters) compared to those who have not (non-seroconverters).
• To identify specific epigenetic modifications associated with viral clearance or immune exhaustion in HBV infection.

Main Methods:

• Genome-wide methylation analysis (RRBS) and gene expression profiling (qRT-PCR) were performed on peripheral blood mononuclear cells (PBMCs).
• Immunophenotyping and cytokine analysis were conducted using flow cytometry and cytokine-bead-array.
• Study included patients with resolved HBV (seroconverters), chronic HBV (non-seroconverters), and healthy controls.

Main Results:

• HBV patients showed significant hypomethylation of immune and metabolic genes compared to controls.
• Seroconverters displayed distinct hypomethylation patterns, including genes like KDM2B and IRF8, and hypermethylation of LAG3 at baseline.
• By week 24, seroconverters showed hypomethylation of IL17RA, IFN-γ, and TGF-β, correlating with increased IL-6 and decreased LAG3, alongside enhanced HBV-specific CD8+ T cell differentiation.

Conclusions:

• Hypomethylation of immune genes in seroconverters suggests an enhanced immune response contributing to viral clearance.
• Non-seroconverters and chronic HBV patients exhibited hypomethylation of LAG3 and TOX, indicating a role in immune exhaustion.