Background: LDL-immune complexes (IC) have a powerful pathogenic role for inducing foam cell formation in vitro more efficiently than any other known mechanism. Studies have also shown that plasma LDL-IC concentration is a powerful marker for the development of atherosclerosis. The structure, fatty acid composition and antioxidant concentrations of Lp(a) and LDL are quite similar. The same oxidation pattern has also been described for both lipoproteins. Modified forms of Lp(a), some resembling oxidized Lp(a), have been identified in human atheromatous lesions. The existence of autoantibodies against MDA-Lp(a) in vivo is also presented. Therefore, we suppose that Lp(a) might trigger an immune response leading to the production of autoantibodies and subsequently to the formation of immune complexes. This study examined the existence of IgG-bound Lp(a)-IC and investigated its value as a risk factor for the development of atherosclerosis.
Methods: We developed two "sandwich" ELISAs for measuring plasma Lp(a)-IC and LDL-IC concentrations, using anti-human IgG(Fab) as the capture antibody, and quantitating with monoclonal anti-apo(a) or anti-apoB enzyme conjugate. Their concentrations were studied in 160 patients with coronary heart disease (CHD) and 290 control subjects.
Results: Plasma TC, LDL-C, TG and apoB concentrations in CHD patients were all significantly increased, whereas HDL-C and apoAI concentrations were decreased. The Lp(a) concentrations in the patients with CHD were also significantly different from those of control (262.4+/-220.0 vs. 211.3+/-199.4 mg/l, P<0.005). Plasma Lp(a)-IC (2.24+/-1.71 vs. 1.62+/-1.50 AU, P<0.0001) and LDL-IC (2.77+/-1.29 vs. 1.40+/-0.92 AU, P<0.0001) concentrations in patients with CHD were both significantly higher than those of control. The relationships between Lp(a)-IC, LDL-IC concentrations and other lipid traits in all the studied subjects (n=450) were carried out. LDL-IC concentrations were positively correlated with LDL-C, apoB, TC, TG and Lp(a) concentrations, while negatively correlated with HDL-C and apoAI concentrations, respectively. Similarly, Lp(a)-IC concentrations were positively correlated with Lp(a), LDL-C, apoB and TC concentrations, while negatively correlated with HDL-C and apoAI concentrations, respectively. Furthermore, a significantly positive relation between LDL-IC and Lp(a)-IC concentrations was also found (r=0.313, P<0.0001).
Conclusions: We report the existence of Lp(a)-IC in both the plasma of patients with CHD and control subjects. Lp(a)-IC concentration increases in the CHD patients.