Circulating antibodies recognizing malondialdehyde-modified proteins in healthy subjects

Antibodies against malondialdehyde (MDA)-modified proteins are often increa sed in patients with diseases related to oxidative stress. However, the cli nical significance of these antibodies is hampered by their frequent presen ce also in healthy controls. Aim of this work has been to characterize the immune reactivity against MDA-derived antigens in healthy subjects. The ser a of 120 healthy subjects contained IgG and IgM targeting MDA-modified huma n albumin (HSA), fibrinogen, and LDL. These sera also displayed weak reacti vity with oxidized LDL and HSA complexed with oxidized arachidonic acid. Co nversely, oxidized HSA or HSA complexed with other aldehydic lipid peroxida tion products was not recognized. Control sera also did not recognize cycli c dihydropyridine-MDA products, while HSA-MDA reactivity was associated (r > 0.9; p < .0005) with the presence of fluorescent lysine-conjugated-imine cross-links. In Western blots both IgG and IgM recognized high molecular we ight HSA-MDA aggregates, but not monomeric HSA-MDA adducts. The addition of sodium cyanoborohydride, that prevented conjugated-imine fluorescence and protein aggregation during HSA-MDA preparation, abolished the antibody bind ing. This suggested that the plasma of healthy subjects contained Ige and I gM recognizing protein aggregates linked through 1-amino-3-iminopropane bri dges. The function of these antibodies is at the moment unknown, but they m ight contribute to scavenging MDA cross-linked proteins. (C) 2001 Elsevier Science Inc.