Circulating antibodies recognizing oxidatively modified low-density lipoprotein in children

The occurrence of circulating antibodies (IgG) against oxidatively modified LDL was investigated in a group of normocholesterolemic, healthy, cardiova scular risk-free children and in a comparable group of normal adults. An in creased titer of IgG recognizing Cu++-oxidized or malondialdehyde (MDA)-der ivatized LDL (MDA-LDL) was a constant feature in children. The antigenic ep itopes recognized by these antibodies were generated rather late in the pro cess of copper-mediated LDL oxidation, concomitantly with the formation of fluorescent adducts between reactive aldehydes (including MDA) and apo B100 , MDA-LDL was not the only antigen recognized: derivatization of other stru cturally unrelated proteins, such as HDL, serum albumin, fibrinogen, and tr ansferrin with MDA led to generation of recognizable epitopes. However, amo ng the various modified proteins, LDL exhibited the highest binding activit y for IgG present in the group of children. This was associated with an enh anced propensity of LDL isolated from children to undergo in vitro oxidatio n, despite normal levels of the endogenous antioxidant alpha-tocopherol. Th ese findings indicate that circulating antibodies recognizing proteins modi fied with end-products of lipid peroxidation (including LDL) are present in healthy cardiovascular risk-free children. The possibility that LDL oxidat ion occurs in vivo already in childhood and may act as the real immunogen i s an attractive but still unproven hypothesis.