Autoimmune responses against oxidant stress and acetaldehyde-derived epitopes in human alcohol consumers

Studies in experimental animals have indicated that chronic ethanol ingestion triggers the formation of antibodies directed against proteins modified with reactive metabolites of ethanol and products of lipid peroxidation. However, the nature and prevalence of such antibodies have not been compared previously in alcoholic patients.

Autoantibodies against adducts with acetaldehyde- (AA), malondialdehyde- (MDA), and oxidized epitopes (Ox) were examined from sera of 54 alcohol consumers with (n = 28) or without (n = 26) liver disease, and from 20 nondrinking controls.

Anti-AA-adduct IgA and IgG antibodies were elevated in 64% and 31% of patients with biopsy-proven alcoholic liver disease (ALD, n = 28), respectively. The IgA titers were significantly higher than those from nondrinking controls (p < 0.001), or heavy drinkers without significant liver disease (p < 0.001). Anti-MDA adduct titers (IgG) were elevated in 70% of the ALD patients. These titers were significantly higher (p < 0.001) than those from nondrinking controls, or heavy drinkers without liver disease. Antibodies (IgG) against Ox epitopes occurred in 43% of ALD patients, and the titers also were significantly higher (p < 0.05) than those from nondrinking controls. The anti-AA and anti-MDA adduct titers in ALD patients correlated significantly with the combined clinical and laboratory index (CCLI) of liver disease severity (r(s) = 0.449, p < 0.05; r(s) = 0.566, p < 0.01, respectively), the highest prevalences of anti-AA-adducts (73%) and anti-MDA-adducts (76%) occurring in ALD patients with cirrhosis.

The present results indicated that autoantibodies against several distinct types of protein modifications are generated in ALD patients showing an association with the severity of liver disease.