Abstract
BackgroundAntibodies 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).Methods226 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.ResultsIncreases 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).ConclusionsHigh 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.
Highlights
Atherosclerosis, the leading cause of cardiovascular disease (CVD), is an inflammatory condition characterized by activated immune competent cells which produce mainly pro-inflammatory cytokines in the lesions [1, 2]
We have reported that natural IgM antibodies against phosphorylcholine are protection factors for atherosclerosis in this cohort, determined by an in house enzyme-linked immunosorbent assay (ELISA) [3], and it is possible that low levels of such antibodies predispose to CVD [2]
When analysed at median levels, we did not determine any role for these markers and atherosclerosis development, except for anti-PC which where the median level differed between groups, making anti-PC a risk marker below the median
Summary
Atherosclerosis, the leading cause of cardiovascular disease (CVD), is an inflammatory condition characterized by activated immune competent cells which produce mainly pro-inflammatory cytokines in the lesions [1, 2]. In systemic lupus erythematosus (SLE), where the risk of CVD and accelerated atherosclerosis is increased, anti-phospholipid antibodies against cardiolipin and phosphatidylserine (anti-CL and anti-PS) have been much discussed and are generally recognized as risk factors for CVD in SLE, typically when present in very high levels as compared to controls. The role of such antibodies in CVD in populations without autoimmune disease as SLE is less clear [2]. Conclusions: High levels of IgM anti-OxPS and anti-OxCL, but not traditional antiphospholipid antibodies (anti-PS and anti-CL), are associated with protection
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