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

Background: Studies in experimental animals have indicated that chronic eth anol ingestion triggers the formation of antibodies directed against protei ns modified with reactive metabolites of ethanol and products of lipid pero xidation. However, the nature and prevalence of such antibodies have not be en compared previously in alcoholic patients. Methods: Autoantibodies against adducts with acetaldehyde- (AA), malondiald ehyde- (MDA), and oxidized epitopes (Ox) were examined from sera of 54 alco hol consumers with (n = 28) or without (n = 26) liver disease, and from 20 nondrinking controls. Results: Anti-AA-adduct IgA and IgG antibodies were elevated in 64% and 31% of patients with biopsy-proven alcoholic liver disease (ALD, n = 28), resp ectively. The IgA titers were significantly higher than those from nondrink ing controls (p < 0.001), or heavy drinkers without significant liver disea se (p, < 0.001). Anti-h IDA adduct titers (IgG) were elevated in 70% of the ALD patients. These titers were significantly higher (p < 0.001) than thos e from nondrinking controls, or heavy drinkers without liver disease. Antib odies (IgG) against Ox epitopes occurred in 43% of ALD patients, and the ti ters 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 li ver disease severity (r(s) = 0.449, p < 0.05; r(s) = 0.566, p < 0.01, respe ctively), the highest prevalences of anti-AA-adducts (73%) and anti-MDA-add ucts (76%) occurring in ALD patients with cirrhosis. Conclusions: The present results indicated that autoantibodies against seve ral distinct types of protein modifications are generated in ALD patients s howing an association with the severity of liver disease.