Acetaldehyde, the main metabolite of ethanol, is a highly reactive species that reacts with macromolecules to produce unstable and stable adducts. Acetaldehyde-modified proteins are immunogenic and have been detected in the liver and blood of alcoholics. Furthermore, antibodies reactive with acetaldehyde-modified proteins have been detected in the plasma of social drinkers and alcoholics. However, the class distribution of immunoglobulins reactive with modified proteins was different in the two groups, being predominantly immunoglobulin (Ig)M in social drinkers, but IgM and IgA in alcoholics. In this study, we demonstrate that heavy drinkers (alcohol intake > 130 g/week for females and 150 g/week for males) also exhibit IgA reactivity with acetaldehyde-modified proteins. The IgA adduct-specific reactivity (IgA reactivity with acetaldehyde-modified bovine serum albumin-reactivity with native bovine serum albumin) showed a moderate correlation with self-reported alcohol intake, but did not correlate with markers such as plasma transaminase, gamma-glutamyltransferase activity, or mean corpuscular volume. IgA adduct-specific reactivity had similar specificity to the conventional tests of alcohol abuse, but had higher sensitivity than the other tests, especially with heavy drinkers. Data presented herein demonstrate that elevated IgA reactivity with acetaldehyde-modified epitopes is associated with heavy drinking and is a potential marker for high alcohol intake.

This work was carried out to elucidate the structures resulting from acetaldehyde-induced modifications at the haemoglobin P-chain N-terminal residues under different experimental conditions. A synthetic peptide (Val-His-Leu-Thr-Pro-Glu-Cys) of d z 798, which represents the six N-terminal residues of the haemoglobin P-chain N-terminus with an additional C-terminal cysteine, was used as a model compound. Peptide-acetaldehyde adducts were separated by reverse-phase HPLC. Fast-atom-bombardment MS and linked-scan (BE) spectra were used to study adduct structures. Under nonreducing conditions at pH 7.4 (1 : 10 peptide/acetaldehyde molar ratio), two types of adducts of m/z 824 were formed, both with modifications at the N-terminal valine. These two adducts were shown to be a Schiff base, and a cyclic 2-methyl-imidazolidine-4-one. The 2-methyl-imidazolidine-4-one adduct was demonstrated to be formed via the Schiff base and to undergo dissociation gradually after 24 h. Reducing conditions at pH 7.4 (peptidelacetaldehyde molar ratio of 1 : 1 with 20 mM NaCNBH,) resulted in the formation of an adduct of d z 826. which was shown to be an N-ethylated adduct of valine. A small amount of nonreduced adducts were also formed under these conditions. Reducing conditions at pH 9.0 (1 : 10 peptidebacetaldehyde molar ratio with 20 mM NaCNBH,) yielded two secondary, i.e. diethylated ( d z 854), products very rapidly.The cysteine residue of the peptide was not found to form an adduct with acetaldehyde under physiological pH.

This study indicates that at least three alcohol-induced haemoglobin adducts occurring in vivo can be measured with promising diagnostic efficiency among women.

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.

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.