Antibodies against Native and Oxidized Cardiolipin and Phosphatidylserine and Phosphorylcholine in Atherosclerosis Development

BACKGROUND Antibodies against cardiolipin and phosphatidylserine (anti-CL and anti-PS) are associated with thrombosis. In contrast, we determined that IgM antibodies against oxidized CL and PS (OxCL and OxPS) and phosphorylcholine (anti-PC) could be protection markers for cardiovascular disease (CVD). METHODS 226 individuals with established hypertension (diastolic pressure>95 mmHg) from the European Lacidipine Study on Atherosclerosis. Antibodies were tested by ELISA. As a surrogate measure of atherosclerosis, the mean of the maximum intima-media thicknesses (IMT) in the far walls of common carotids and bifurcations was determined by ultrasonography at the time of inclusion and 4 years following inclusion. RESULTS Increases in IMT measures at follow-up were significantly less common in subjects which at baseline had high IgM anti-OxPS and anti-PC at above 75th percentile: OR 0,45, CI (0,23-0,86) and OR 0.37, CI (0,19-0,71), p = 0.0137 respectively and above 90th percentile: OR 0.32, CI (0,12-0,84) and OR 0.39, CI (0,15-1.00), p = 0.050 and OR 0,22, CI (0,08-0,59) p = 0,0029. IgM anti-OxCL was negatively associated with IMT increases (OR, 0.32, CI (0,12-0,84), p = 0231). There were no associations for IgM anti-PS or anti-CL. Anti-PC, as determined herein by a commercial ELISA, was strongly associated with data from our previously published in house ELISA (R = 0,87; p<0,0001).) Anti-PC was also a risk marker at low levels (below 25th percentile; OR = 2,37 (1,16-4,82), p = 0,0177). CONCLUSIONS High levels of IgM anti-OxPS and anti-OxCL, but not traditional anti-phospholipid antibodies (anti-PS and anti-CL), are associated with protection against atherosclerosis development. In addition, low IgM anti-PC was a risk marker but high a protection marker.