Circulating Antibodies Recognizing Oxidatively Modified Low-Density Lipoprotein in Children

Abstract

The occurrence of circulating antibodies (IgG) against oxidatively modified LDL was investigated in a group of normocholesterolemic, healthy, cardiovascular risk-free children and in a comparable group of normal adults. An increased titer of IgG recognizing Cu++-oxidized or malondialdehyde (MDA)-derivatized LDL (MDA-LDL) was a constant feature in children. The antigenic epitopes recognized by these antibodies were generated rather late in the process 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 structurally unrelated proteins, such as HDL, serum albumin, fibrinogen, and transferrin with MDA led to generation of recognizable epitopes. However, among the various modified proteins, LDL exhibited the highest binding activity for IgG present in the group of children. This was associated with an enhanced propensity of LDL isolated from children to undergo in vitro oxidation, despite normal levels of the endogenous antioxidant alpha-tocopherol. These findings indicate that circulating antibodies recognizing proteins modified with end-products of lipid peroxidation (including LDL) are present in healthy cardiovascular risk-free children. The possibility that LDL oxidation occurs in vivo already in childhood and may act as the real immunogen is an attractive but still unproven hypothesis.

Are Anti–Oxidized Low-Density Lipoprotein Antibodies Pathogenic or Protective?

“…As mentioned previously, the binding activity of anti-oxLDL IgG is significantly higher in children than in adults. 48 These studies seem to support the idea that anti-oxLDL antibodies have a protective function against the development of atherosclerosis and CVD in healthy individuals. Table 3 lists [85][86][87][88][89][90][91][92][93][94] several studies that found negative associations between anti-oxLDL antibodies and CVD and other conditions.…”

“…These antibodies have been found in children, 48 healthy adults, and patients with coronary heart disease. 27 Circulating antibodies recognizing oxLDL are present in cardiovascular risk-free children.…”

“…27 Circulating antibodies recognizing oxLDL are present in cardiovascular risk-free children. The levels of the antibody in children are significantly higher than in adults, 48 suggesting that the antibodies may not necessarily be related to atherosclerosis and CVD. It is probable that the high levels of antibodies in children modulate the antigen and thus protect against the development of atherosclerosis and CVD.…”

Relationship of Oxidized Phospholipids and Biomarkers of Oxidized Low-Density Lipoprotein With Cardiovascular Risk Factors, Inflammatory Biomarkers, and Effect of Statin Therapy in Patients With Acute Coronary Syndromes

“…4) They display an acute phase response in acutely ill patients, often increasing significantly within hours to days after an event. 5) They may have different influences on atherogenesis, at least in experimental models, in which IgMs, which are more likely to be enriched in natural antibodies present even at birth (26) seem to be atheroprotective, but IgGs seem to be atherogenic, except perhaps in response to vaccination, in which they may be associated with atheroprotection (10,26,34,35,(37)(38)(39). In humans, we have recently shown that IgM OxLDL autoantibodies and IgM apoB-ICs were associated inversely with the presence of angiographically determined CAD, whereas IgG OxLDL autoantibodies and IgG apoB-ICs were positively associated (40).…”

Phosphorylcholine-Dependent Cross-Reactivity between Dental Plaque Bacteria and Oxidized Low-Density Lipoproteins

“…The finding that PC is a common component of plaque bacteria and that patients with attachment loss have elevated antibody levels against PC therefore argue that the anti-PC response is a common tie between many systemic conditions and periodontal infections. It is also noteworthy that some investigators have reported that anti-oxLDL antibodies are present in newborns and children and increase during childhood (21). It has been speculated that such antibodies may reflect oxidative damage to LDLs; however, a portion of such antibody could reflect exposure to the oral flora during inflammatory episodes.…”