Comparison of Carbohydrate‐Deficient Transferrin, Immunoglobulin A Antibodies Reactive with Acetaldehyde‐Modified Protein and Acetaldehyde‐Modified Albumin with Conventional Markers of Alcohol Consumption

Abstract

Carbohydrate-deficient transferrin (CDT) has emerged as the best new marker for alcohol abuse. Recently plasma immunoglobulin A (IgA) reactivity with acetaldehyde (AcH)-modified proteins, or the modified proteins per se, have been proposed as a markers for high levels of alcohol consumption. In this study, we have compared CDT, IgA reactivity with AcH adducts (IgA ASR), and AcH-modified albumin with conventional markers of high alcohol intake in groups with well-defined drinking histories. The plasma activity of ALT, AST, and gamma-glutamyltransferase increased steadily with increasing alcohol consumption. CDT and AcH-modified albumin showed a similar pattern, whereas IgA ASR appeared only to be elevated after a threshold level of consumption had been reached. Neither CDT IgA ASR or AcH-modified albumin correlated strongly with any of the conventional markers or each other. This study shows that CDT, IgA ASR, AcH-modified albumin, and the conventional markers are not related, but suggests that the concurrent use of CDT and IgA ASR may lead to better identification of high alcohol intake.

Liabilities Associated with the Formation of “Hard” Electrophiles in Reactive Metabolite Trapping Screens

“…These observations suggest that the mechanism of hepatic GSH depletion involves the reaction of the ethanol metabolite acetaldehyde with the GSH breakdown product Cys-Gly to yield 2-(methylthiazolidine-4-carbonyl)­glycine derivative (Scheme ). ,, The thiazolidine conjugate has been detected in rat bile after chronic ethanol treatment, which incidentally led to high systemic acetaldehyde concentrations (∼50 μM), comparable to the values (∼100 μM) observed in some Japanese alcoholic patients. , Administration of large doses of l -cysteine or the thiol-based chelator d -penicillamine effectively protects ethanol-treated rats against acetaldehyde toxicity with the concomitant formation of the anticipated cyclized condensation product between d -penicillamine and acetaldehyde. − Nonenzymatic conjugation of acetaldehyde with a free α-amino terminus, ε-amine side groups of lysine residues, and sulfhydryl groups in proteins (e.g., hemoglobin and serum albumin) have been reported in vitro and in vivo in alcoholics. − Conjugates of acetaldehyde with proteins trigger the generation of antibodies against de novo acetaldehyde epitopes. , Quantification of acetaldehyde–protein conjugates, directly or via their antibodies, has been used to evaluate chronic alcohol intake. ,, …”