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Published on: February 19, 2019
Changes in gene expression in liver tissue from patients with fulminant hepatitis E
Anshu Naik1, Amit Goel1, Vinita Agrawal1
1Anshu Naik, Amit Goel, Aditya N Sarangi, Nanda Chhavi, Rakesh Aggarwal, Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
Fulminant hepatitis E patients exhibit increased CD8(+) T cell infiltration and gene expression related to cytotoxic T cell pathways in the liver. This suggests a potential role for these immune cells in the disease
Area of Science:
- Hepatology
- Immunology
- Molecular Biology
Background:
- Fulminant hepatitis E (FH-E) is a severe liver disease with high mortality.
- Understanding the host immune response in FH-E is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate host gene expression profiles in liver tissue from FH-E patients.
- To quantify immune cell populations, specifically CD4(+), CD8(+), and CD56(+) cells, within FH-E liver tissues.
- To compare these findings with those from fulminant hepatitis B (FH-B) and healthy liver controls.
Main Methods:
- Microarray analysis (Illumina Human WG-6_v3_BeadChip) of post-mortem liver tissues from FH-E, FH-B, and healthy individuals.
- Differential gene expression analysis using stringent statistical criteria (≥ 2.0-fold change, FDR < 0.05).
- Validation of key gene expression changes using quantitative reverse transcription PCR (qRT-PCR).
- Gene Ontology and pathway analysis (DAVID server) to identify biological processes and pathways.
- Immunohistochemical staining for CD4(+), CD8(+), and CD56(+) cells, followed by cell counting.
Main Results:
- Significant differential gene expression was observed in FH-E and FH-B livers compared to controls, with substantial overlap in metabolic, hemostatic, and complement pathways.
- FH-E livers, unlike FH-B, showed activated immune response pathways, particularly those involving cytotoxic T cells.
- qRT-PCR confirmed microarray findings for selected genes in FH-E.
- Immunohistochemistry revealed a significant increase in CD8(+) T cells in the livers of both FH-E and FH-B patients compared to controls.
Conclusions:
- Fulminant hepatitis E is characterized by CD8(+) T cell infiltration in the liver.
- Increased gene expression of cytotoxic T cell pathways in FH-E livers suggests a significant pathogenetic role for these immune cells.
- These findings highlight the involvement of cellular immunity in the pathogenesis of severe hepatitis E.
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