Antibodies Against Oxidized LDL and Carotid Artery Intima-Media Thickness in a Healthy Population

Abstract

Abstract-Oxidation of LDLs plays an important role in atherosclerosis, and immune response to oxidized LDL (oxLDL) may modulate atherogenesis. Although immunization with oxLDL is shown to suppress atherogenesis in animal models, the role of the immune response to oxLDL is not well established in humans. We investigated the relationship between the titer of anti-oxLDL antibody (oxLDL Ab) and arterial wall thickness in a healthy population with no clinical signs of atherosclerosis. Intima-media thickness of the carotid arteries (CA-IMT) was measured by high-resolution B-mode ultrasonography in 446 healthy subjects. The titer of IgG-class oxLDL Ab was measured by a solid-phase ELISA. In univariate analysis, CA-IMT correlated positively with age, systolic blood pressure, total cholesterol, triglyceride, LDL cholesterol, body mass index, and waist-to-hip ratio, whereas it correlated negatively with HDL cholesterol and oxLDL Ab titer. The inverse association between oxLDL Ab titer and CA-IMT remained significant in multiple regression analysis, which took other confounding variables into account. These results indicate an independent inverse relationship between oxLDL Ab titer and CA-IMT in healthy subjects, supporting the hypothesis that immune response to oxLDL may have a protective role at an early stage of human atherosclerosis.

Association Between IgM Against an Aldehyde-Modified Peptide in Apolipoprotein B-100 and Progression of Carotid Disease

“…The results of several subsequent studies have been inconsistent reporting that antibodies against MDA-or oxidized LDL are increased in patients with coronary artery disease, 34 -36 predict risk for development of myocardial infarction, 37 have no association with coronary artery disease, 38,39 increase with severity of carotid disease, 40 and decrease with severity of femoral disease 40 and carotid disease. [41][42][43] The approach used in the present study to analyze antibodies against one clearly defined antigen present in oxidized LDL may offer the advantage of a higher specificity and reproducibility. A limitation of this technique is that only a fraction of all antibodies against epitopes in oxidized LDL are measured.…”

Protective autoantibodies: Role in homeostasis, clinical importance, and therapeutic potential

“…Immunization of mice with MDA-modified LDL induced the expansion of innate B-1 cells and the secretion of IgM antibodies that bind the PC of oxPLs, thus reducing atherogenesis (42). Anti-oxLDL antibodies have been shown to be inversely related to intima-media thickening (IMT) of the carotid arteries when studied in a healthy population with no clinical signs of atherosclerosis (43). In a population-based cohort of 1,022 middle-age men and women, the relationship between different isotypes of autoantibodies to copper-oxidized LDL and MDAmodified LDL and the development of carotid artery IMT was investigated (44).…”

Antibodies Against β2‐Glycoprotein I Complexed With an Oxidised Lipoprotein Relate to Intima Thickening of Carotid Arteries in Primary Antiphospholipid Syndrome

“…However, data contrast on this issue. One study described an inverse and independent relationship between anti-oxLDL titre and IMT of carotid arteries in healthy subjects (Fukumoto et al 2000), whereas, IgG-oxLDL titre positively associated with IMT of the CC artery in another study (Hulthe et al 2001). That is, both the antigen and the corresponding antibody seem to have a relation with IMT.…”