Antibodies to Oxidized LDL and LDL-Containing Immune Complexes as Risk Factors for Coronary Artery Disease in Diabetes Mellitus

High Levels of (Un)Switched Memory B Cells Are Associated With Better Outcome in Patients With Advanced Atherosclerotic Disease

“…However, IgG‐α‐oxLDL titers were not associated with the occurrence of secondary CVD events, suggesting that oxLDL antibodies are not responsible for the protective effect of memory B cells in our population of severe atherosclerotic patients. These data are in line with other observations that also show no association with secondary CVD events,54, 55 but do not corroborate with other studies showing oxLDL antibodies to be associated with occurrence and severity of CVD 34, 35, 36, 37. Apart from their pivotal role in antibody generation, B cells can also regulate T‐cell responses and produce cytokines, suggesting a more‐intricate role in cardiovascular disease 14, 56…”

Atherogenesis and the humoral immune response to modified lipoproteins

“…These authors purified oxLDL and the corresponding IgG antibodies from atheromatous lesions of humans and Watanabe hyperlipidemic rabbits, thus demonstrating that the ingredients necessary for the formation of LDL-IC are present in the damaged arterial wall. Several groups, including ours, have reported a significant correlation between soluble LDL-IC and the presence of CAD [37,38,43]. Orekhov and coworkers reported that the level of cholesterol in isolated circulating IC, which reflects the amount of LDL-IC in circulation, correlated with the severity of coronary atherosclerosis [43,44].…”

“…The results of these studies were rather disappointing, because the results were often conflicting and failed to produce a clear cut indication of the clinical value of modified lipoprotein antibody assays as biomarkers for the development and/or progression of atherosclerosis. While some groups reported a positive correlation between the levels of oxLDL antibodies and different endpoints considered as evidence of atherosclerotic vascular disease, such as progression of carotid atherosclerosis or risk for the future development of myocardial infarction [21][22][23][24][25][26][27], others failed to show such correlation or showed an inverse correlation [28][29][30][31][32][33][34][35][36][37][38].…”

“…Thus, the measurement of free circulating autoantibodies depends not only on the magnitude of the antibody response but also on antibody avidity and on the amount of antigen present in circulation. If the average avidity of circulating autoantibody is sufficiently high and antigen is present in circulation, soluble IC are formed and in their presence the assays for serum oxLDL antibody concentrations become inaccurate and underestimate the absolute concentration of circulating oxLDL antibody [38,39]. The characterization of purified oxLDL and AGE-LDL antibodies gave a further impetus to the study of their potential pathogenic role.…”

“…Turk et al reported that the concentrations of Apo-B in circulating IC was significantly higher in patients with coronary heart disease [45]. A prospective study involving 98 diabetic subjects recruited as part of the Pittsburgh EDIC study showed that LDL-IC and oxLDL antibodies, correlated with the development of coronary artery disease [CAD] over a period of seven years, but while the correlation with LDL-IC levels was direct, the correlation with oxLDL antibody levels was inverse [37,38]. To further evaluate the validity of the hypothesis that modified LDL (mLDL)-IC play a pathogenic role in diabetes we screened 1050 patients from the DCCT/EDIC cohort for mLDL-IC and evaluated the impact of these IC in progression of carotid intima-media thickness [IMT], a surrogate marker for CAD.…”