Maternal Immunity Influences Vertical Transmission of Hepatitis B to Newborns ( PI: Dr. Nirupma Trehanpati, Co- P I: Prof. Shiv K. Sarin, Dr. Sharda Patra, Ph.D student Ashish Kumar)
Mother to child transmission (MTCT) of Hepatitis B virus (HBV) is one of the major routes of transmission during pregnancy and is responsible for 90% chance of infection acquired by infants. Globally about 400 million people are infected with HBV.
The prevalence rate of HBsAg positivity in pregnant women in India varies from 1–9%and HBeAg positivity vary from4.8–68.7%. Vertical transmission of hepatitis B virus (HBV) fromthemother to the newborn often results in viral persistence. Laboratory of molecular immunology is working from last one decade to understand the mechanisms of maternofetal HBV transmission.Maternal high viral load, hepatitis B e antigen (HBeAg) and HBsAg levels are associated with HBV transmission to newborns. Other than this, humoral and adaptive immune responses are also equally important for clearance of pathogens and long-term immunity. A subset of CD4+ T cells and T follicular helper (TFh) cells play a key role in regulation of B-cell-mediated responses. TFh cells and B cells also help in HBsAg and HBeAg seroconversion. The work, suggests a significant role of maternal immunity in the vertical transmission of Hepatitis B Virus.
Early Antiviral Treatment (Tenofovir) Declines Hepatitis B Viral Loadwith Emergence of Functional T Cells with reduced PD1 expression in HBsAg Positive Pregnant Females ( PI: Dr. Nirupma Trehanpati, Co- P I: Prof. Shiv K. Sarin, Dr. Sharda Patra, Ph.D studentAshish Kumar, JRF: PoojaNegi)
The pathogenesis of chronic hepatitis B in pregnant women, including changes in cellular immune response to the virus, is mostly unexplored. Virus-specific CD4+ helper and CD8+ cytotoxic T cells are critical for spontaneous resolution of hepatitis B virus (HBV) infection. These cellular immune responses are severely compromised in HBV infections that persist. HBV flares at delivery reconstitute immunity in HBsAg+ve pregnant females, however there is little data of immune reconstitution during kinetics of pregnancy in HBsAg+ve pregnant females with or without anti-viral therapy.We have observed HBV DNA flares in both groups however, there was continues decline in HBV DNA, HBsAg levels throughout the pregnancy in treated pregnant females than non-treated ones. In fact,we have observed significant reduction in HBsAg quant at the time of delivery in treated patients. Together with decreased expression of exhaustionmarker PD1 on Cd4+ and CD8+T cells in tenofovir treated females compared to non-treated. Furthermore, they also had higher HBV specific IFN- , IL-17Aand decreased IL-10 and TGF- secreting CD4 and CD8 T cell. Alongwith increased HBV specific T cells, antibody secreting plasma B cells were also increased in treated females. Therefore, it was concluded that early start of anti-viral treatment inHBsAg positive pregnant females, reconstitute immunity better and could prevent viral flares postpartum.
Promoter methylation of suppressive genes impairs function of Tregs and effector cells in non-seroconverters after hepatitis B reactivation ( P I:Dr.Nirupma Trehanpati, Co-P I :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.Wehave analysed the whole blood immune scan in chronic hepatits B patients and reactivation patients. Methylation status of inhibitory genes (Foxp3, TGF- , 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 promotermethylation profile similar to that of healthy subjects ( Presented atAASLD, 2018) .
Immune exhaustion and Immune modulation in patients with cirrhosis and sepsis and development of liver Failure (PI: Dr. Nirupma Trehanpati, Dr. Shiv K Sarin, Ph.D students: Rashi Sehgal and Varsha Diwedi)
End-stage chronic liver disease afflicts millions of people worldwide. Sepsis in cirrhosis are the one of the major caused of mortality. The progression of sepsis in cirrhotic patients is due to overwhelming immune disbalance, cytokine release. It is likely that a state of immunoparesis develops due to a switch from immune activation to immune exhaustion. Our aim is to understand the cirrhosis associated immune deficiency and immune cell exhaustion in patients with acute on chronic liver failure.