ANTIBODIES MADE AGAINST A FORMALDEHYDE PROTEIN ADDUCT CROSS-REACT WITH AN ACETALDEHYDE-PROTEIN ADDUCT - IMPLICATIONS FOR THE ORIGIN OF ANTIBODIES IN HUMAN SERUM WHICH RECOGNIZE ACETALDEHYDE-PROTEIN ADDUCTS

Acetaldehyde, the major metabolite of ethanol, reacts with lysine and other free amino groups on proteins to form acetaldehyde-protein adduc ts. The presence of antibodies which recognize such acetaldehyde-prote in adducts in sera from alcoholics has been attributed to an immune re sponse to such adducts. Complicating this conclusion is the finding th at sera from non-alcoholic control subjects also contain antibodies wh ich recognize acetaldehyde-protein adducts. In the current research we sought to determine whether antibodies which recognize epitopes forme d by the reaction of a protein with acetaldehyde can be formed in resp onse to a protein modified with a structurally related protein adduct. We modified lysine residues on apolipoprotein (ape) B-100 with acetal dehyde and formaldehyde under reducing conditions, to form epsilon-N-m ethyl- and epsilon-N-ethyl-lysine residues, and with acetic anhydride to form epsilon-N-acetyl-lysine residues, and made antibodies against these modified proteins in guinea-pigs. In ELISA assays antibodies mad e against methylated apoB-100 (Me-apoB) cross-reacted effectively with ethylated apoB-100 (Et-apoB), while antibodies made against acetic an hydride-modified apoB-100 did not cross-react. We conclude that methyl -lysine shares one or more immunoreactive epitopes with ethyl-lysine, and that antibodies which recognize acetaldehyde-modified proteins can be formed in response to formaldehyde-modified proteins. We demonstra te that sera from both alcoholics and non-drinkers contain antibodies which recognize Me-apoB and Et-apoB and that the titres of these antib odies are comparable. These data raise the possibility that some human serum antibodies which recognize acetaldehyde-modified protein epitop es may have been made against formaldehyde-modified protein epitopes. These data also illustrate the difficulty in assigning a unique causal relationship between the presence of an antibody, and the immunogen r esponsible for the formation of such antibody.