Characterization of soluble FAS, FAS ligand and tumour necrosis factor-alpha in patients with chronic HCV infection.
BACKGROUND
There are limited reports on the role of the cell surface receptor Fas and its ligand molecule in mediating apoptosis during infection with the hepatitis C virus (HCV).


OBJECTIVE
The aims of this study were (1) to assess the susceptibility of the Fas antigen expressed on peripheral blood mononuclear cells to Fas ligand-induced-death in patients with chronic HCV infection and (2) to investigate the correlation between the plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), tumour necrosis factor-alpha (TNF-alpha), alanine amino transferase (ALT), and HCV viral load.


METHODS
The susceptibility of peripheral blood mononuclear cells from 17 subjects with chronic HCV infection to Fas ligand induced cell death was assessed using a water soluble tetrazolium assay. The plasma levels of associated markers such as sFas, sFasL, and TNF-alpha were quantified using immunoassays. ALT values were obtained from hospital records. Viral loads were quantified using a commercially available quantitative assay--the Amplicor Monitor (version 2.0). Controls for comparison included a group of healthy individuals and individuals infected with the human immunodeficiency virus 1.


RESULTS
The percentage of cell death induced in hepatitis C virus infected individuals was lower than that seen in the healthy control group. Patients infected with HCV had higher average values of sFas and TNF-alpha as compared to both control groups. Plasma levels of sFas in patients with chronic HCV infection showed significant positive correlations to ALT and TNF-alpha levels. TNF-alpha levels also showed a significant positive correlation with ALT levels.


CONCLUSIONS
PBMC in HCV infection exhibit decreased susceptibility to Fas ligand induced cell death. This may signify a means by which HCV escapes immune surveillance. This phenomenon merits further investigation. The strong correlations observed between plasma sFas, ALT and TNF-alpha suggest a potential role for these markers as an alternative to an invasive liver biopsy.
Raghuraman
Sukanya
S
Department of Clinical Virology, Christian Medical College, Vellore 632004, TamilNadu, India. sukanyarr@yahoo.com
Abraham
Priya
P
Daniel
Hubert Darius
HD
Ramakrishna
B S
BS
Sridharan
Gopalan
G
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D016923:Cell Death; D053222:Fas Ligand Protein; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000473:pathology; D015497:HIV-1; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000473:pathology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000097:blood*; D019014:fas Receptor / Q000097:blood*
D015415:Biomarkers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D019014:fas Receptor