Hepatic Cell Biology
Promoter methylation of suppressive genes impairs function of Tregs and effector cells in non-seroconverters after hepatitis B reactivation (PI: Dr. Nirupma Trehanpati, Co-PI: Dr. Gayatri Ramakrishna, Ph.D student Mojahidul Islam )
Hepatitis B surface antigen (HBsAg) seroconversion is common in reactivation patients, probably due to immune reconstitution. Primarily, termination of tolerance is decided by suppressive and inhibitory markers leading to restoration of immune responses. We have analysed the whole blood immune scan in chronic hepatits B patients and reactivation patients. Methylation status of inhibitory genes (Foxp3, TGF-β, and PD1) was also checked in patients to determine its predictive value. Immunoprofiling of seroconverted HBVr patients revealed higher CD4+, CD8+ counts and lower expression of PD1 at baseline (CD3 p=0.0277, CD4 p=0.0240, CD8 p=0.0088, CD19 p=0.0110) than HBVr non-seroconverters. Though there was no significant difference in numbers of CD4 Tregs in two groups, but there was significant decrease in CD8 Tregs (CD8+CD25+ p=<0.05, CD8+CD25+CD127lo/-Foxp3+. Fate of seroclearance in CHBV reactivation patients depends upon baseline CpG methylation status of PDCD1 genes. The seroconverters showed promoter methylation profile similar to that of healthy subjects ( Presented at AASLD, 2018) .