Acetaldehyde adducts and autoantibodies against VLDL and LDL in alcoholics.
Alcohol consumption markedly increases the hepatic output of very low density lipoprotein (VLDL), whereas it decreases the resulting low density lipoprotein (LDL) levels and apolipoprotein B. As ethylation of apoB-lysine renders LDL immunogenic and accelerates their clearance, and as alcoholics develop antibodies against acetaldehyde-protein adducts, we searched for antibodies against lipoproteins. We measured serum IgG, IgA, and IgM titers against VLDL, LDL and high density lipoprotein (HDL) in 10 non-alcoholics and 35 recently drinking alcoholics by ELISA assay. Alcoholics had higher IgG titers than non-alcoholics against VLDL and LDL; these were higher with VLDL than LDL or HDL. Using VLDL and LDL (but not HDL) from alcoholics gave the greatest response. There was no difference in IgA and IgM reactivity. To search for acetaldehyde adducts, we measured the reactivity of VLDL, LDL, HDL, and residual serum proteins against a rabbit anti P4502E1-acetaldehyde adduct IgG, which recognizes the adducts but not the unmodified proteins (except for P4502E1). ApoB-containing lipoproteins from alcoholics (and to a lesser extent non-lipoprotein proteins) reacted with anti-adduct IgG more strongly than those of non-alcoholics. The difference was striking for VLDL, less for LDL, and not detectable for HDL. This suggests that acetaldehyde reacts with apoB prior to its secretion from the liver and that the altered VLDL are partially removed prior to their conversion to LDL. In conclusion, alcoholics develop acetaldehyde adducts in apoB-containing lipoproteins, particularly VLDL. The immune response to these neoantigens could result in accelerated clearance of VLDL and LDL and decreased conversion of VLDL to LDL.
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, NY 10468.
H
H
Wehr
M
M
Rodo
C S
CS
Lieber
E
E
Baraona
D000079:Acetaldehyde / Q000276:immunology*; D000437:Alcoholism / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D006801:Humans; D008074:Lipoproteins / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000276:immunology*; D008079:Lipoproteins, VLDL / Q000276:immunology*
D001323:Autoantibodies; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D000079:Acetaldehyde