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Oxidative Stress as a Trigger for Cellular Immune Responses in Patients with Alcoholic Liver Disease

Lookup NU author(s): Dr Stephen Stewart, Professor Chris Day, Professor David Jones


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Serum antibodies reactive with neo-antigens generated during ethanol metabolism have been identified in patients with alcoholic liver disease (ALD), although their role in the pathogenesis of disease remains unclear. In this study, we characterized peripheral blood mononuclear cell (PBMC) T-cell and antibody responses to human serum albumin (HAS) adducted with acetaldehyde under reducing conditions (AcA-HSA) or with malondialdehyde (MDA-HSA) in patients with advanced ALD (AALD, n = 28), heavy drinkers with no liver disease (NALD, n = 14), and mild/moderate drinking controls (n = 22). Peak proliferative responses of PBMC were assessed in vitro by tritiated thymidine incorporation after the addition of optimized concentrations of antigen or OKT3. Antibody titers were determined by enzyme-linked immunosorbent assay (ELISA). MDA-HSA induced PBMC T-cell proliferation was significantly higher in ALD than in NALD or control patients. Moreover, 10 of 28 (36%) of ALD patients had significant T-cell proliferative responses to MDA-HSA compared to 0 of 14 (0%, P = .02) of the NALD group and 2 of 22 (9%, P < .05) of controls. No significant difference in PBMC T-cell response to Aca-HSA was seen between subject groups. Patients with positive cellular responses to MDA had higher serum anti-MDA antibody titers than those not exhibiting a positive cellular response (P < .005). In conclusion, the pattern of cellular and humoral responses to MDA adducts suggests that the development of these responses may be a susceptibility factor for the development of advanced alcoholic liver disease. The apparent importance of T-cell responses to MDA adducts suggests that oxidative stress may represent an important stimulus for the development of cellular immune responses associated with advanced ALD.

Publication metadata

Author(s): Stewart SF, Vidali M, Day CP, Albano E, Jones DEJ

Publication type: Article

Publication status: Published

Journal: Hepatology

Year: 2004

Volume: 39

Issue: 1

Pages: 197-203

ISSN (print): 0270-9139

ISSN (electronic): 1527-3350

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/hep.20021

PubMed id: 14752838


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