Role of Innate Immune Regulatory Genes, FOXP3 and FOS in Chronic Hepatitis B Infection

Biswajyoti Borkakoty1, Mandakini Das Sarmah1, Tapan Majumdar2

  • 1Regional VRDL, ICMR-Regional Medical Research Centre, NE Region, Dibrugarh, India.

Viral Immunology
|May 17, 2022
PubMed

Insights

Chronic hepatitis B (CHB) involves immune dysregulation, with FOS and FOXP3 genes upregulated in HBeAg-positive CHB. Targeting these genes may improve CHB management and prevent liver cancer.

Area of Science:

  • Immunology
  • Hepatology
  • Genetics

Background:

  • Hepatitis B virus (HBV) infection leads to chronic hepatitis B (CHB), a major cause of liver disease and mortality worldwide.
  • The precise mechanisms driving HBV persistence and CHB remain incompletely understood.
  • Immune regulatory genes are hypothesized to play a role in the progression of CHB.

Purpose of the Study:

  • To investigate the role of immune regulatory genes in chronic hepatitis B (CHB) compared to spontaneously cleared HBV infection.
  • To identify potential genetic markers associated with CHB persistence and its sequelae.

Main Methods:

  • A case-control study involving 679 subjects from Northeast India.
  • Real-Time Polymerase Chain Reaction Array used to analyze the relative gene expression of 26 innate immunity genes.
  • Subjects categorized into CHB with HBeAg(+), CHB with HBeAg(-), spontaneously cleared HBV, and healthy controls.

Main Results:

  • Proto-oncogene FOS was upregulated in CHB with HBeAg(+) (2.3-fold) and significantly in hepatocellular carcinoma (4.1-fold).
  • FOXP3 gene showed significant upregulation (3.0-fold) in CHB with HBeAg(+) compared to spontaneously cleared HBV infection.
  • A higher prevalence of CHB was observed in men (66.4%) than in women (33.6%).

Conclusions:

  • CHB with HBeAg positivity is characterized by a disrupted immune response, evidenced by the upregulation of FOS and FOXP3 genes.
  • Early induction of HBeAg seroconversion, potentially with FOS inhibitors, could offer new therapeutic strategies for CHB.
  • These findings have clinical implications for managing CHB and preventing liver cirrhosis and hepatocellular carcinoma (HCC).

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