Alcohol Dehydrogenase: An Autoantibody Target in Patients with Alcoholic Liver Disease

Abstract

The link between alcohol consumption and liver disease is not direct and several factors including autoimmunity to hepatocyte components have been implicated. We have previously identified alcohol dehydrogenase (ADH) as an autoantigen in autoimmune liver disease and in a proportion of patients with alcoholic liver disease. The aim of the present study is to investigate the association between the presence of anti-ADH antibodies, alcohol consumption and severity of liver damage in alcoholic patients. The presence of antibodies to human ADH β2 and horse ADH was investigated in 108 patients with documented history of alcohol consumption and alcohol related liver disease, 86 being active alcohol abusers and 22 on sustained alcohol withdrawal, 39 with non-alcohol related disease and 22 normal subjects. Antibodies to either ADH form were more frequently detected in active alcohol abusers (55/86, 64%) than in patients on sustained alcohol withdrawal longer than 6 months (1/8, 13%, p<0.005), HBV infection (2/8, 25%, P=0.03), non-alcohol related disease (9/29, 23%, p<0.0001) and in normal controls (3/22, 14%, p<0.0001); were more frequent in patients with cirrhosis than in those with steatosis (26/34, 76% vs 34/64, 53%, P=0.02); and were associated with elevated levels of ALT (anti-ADH β2, p<0.05), immunoglobulin A (p<0.05) and γ-glutamyl transpeptidase (P=0.01). Anti-ADH antibody positive serum samples were able to inhibit the enzymatic activity of ADH. These findings suggest that anti-ADH antibodies may be triggered by alcohol consumption and act as a disease activity marker in alcoholic liver disease.