COLLAGEN-ACETALDEHYDE ADDUCTS IN ALCOHOLIC AND NONALCOHOLIC LIVER-DISEASES

Alcoholic and, to a lesser extent, nonalcoholic patients with liver di sease have serum antibodies to acetaldehyde-protein adducts produced i n vitro. These antibodies presumably reflect the presence of adducts i n the liver, but the protein that triggers this immune response has no t been identified. To study this, we measured the reactivity of cytoso lic proteins to rabbit IgG developed against a P-450 2E1-acetaldehyde adduct, isolated from alcohol-fed rats, that recognizes acetaldehyde-m odified epitopes in proteins. Adducts were determined on Western blots by scanning densitometry of antibody-linked alkaline phosphatase acti vity in 4 normal livers and in needle biopsy specimens from subjects w ith liver disease, 17 alcoholic and 14 nonalcoholic. In all livers, ex cept for a normal one, we found a reactive protein of at least 200 kD, similar to the collagen-acetaldehyde adduct we reported to be markedl y increased in rats with experimentally induced cirrhosis. The immunos taining intensity in the alcoholic patients with liver disease was eig htfold (p < 0.01) and that in nonalcoholic patients with liver disease was fourfold, greater (p < 0.02) than the weak staining in normal liv ers; it correlated with the degree of inflammation and serum AST or ga mma-glutamyl transpeptidase activities. The adduct was reproduced on i ncubation of normal cytosolic proteins with 2.5 mmol/L acetaldehyde, w hereas higher concentrations yielded many additional adducts; the addu ct also reacted with IgG antibody to rat collagen type I and disappear ed after digestion with collagenase, suggesting that the target protei n is a form of collagen. The association of this collagen-acetaldehyde adduct with parameters of liver disease activity suggests that the ad duct reflects the liver injury and may even contribute to its developm ent, both in alcoholic and in nonalcoholic subjects.