Natural antibodies to oxidation‐specific epitopes: innate immune response and venous thromboembolic disease |
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| Authors: | S Eichinger PA Kyrle M Kammer L Eischer M Ozsvar Kozma C J Binder |
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| Institution: | 1. Department of Medicine I, Medical University of Vienna, Vienna, Austria;2. Karl Landsteiner Institute for Clinical Thrombosis Research, Vienna, Austria;3. Section for Clinical Biometrics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria;4. Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria;5. Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria |
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| Abstract: | Essentials - Natural antibodies to oxidation‐specific epitopes have antithrombotic properties.
- We evaluated the relation between natural IgM and IgG antibodies and the venous thrombosis risk.
- Risk of recurrent thrombosis was higher in patients with low natural IgM antibody levels.
- The protective effect of high IgM levels suggests a role of innate immune response in thrombosis.
Summary Background and objectives Natural antibodies to oxidation‐specific epitopes protect from atherothrombotic events. Whether mechanisms of innate immunity are relevant in the pathogenesis of venous thromboembolism (VTE) is unknown. Patients/Methods We measured plasma levels of immunoglobulin M (IgM) antibodies to oxidized low‐density lipoproteins (OxLDL) and phosphocholine (PC) by enzyme linked immune assay in 663 patients with unprovoked VTE, who were prospectively followed after discontinuation of anticoagulation for a median of 8.8 years. The study endpoint was recurrent VTE. Results IgM antibody levels to OxLDL and PC were higher in patients without compared to those with recurrent VTE (n = 174, 26.2%). For each doubling of OxLDL‐IgM or PC‐IgM the hazard ratio (HR) of recurrence was 0.88 (95% confidence interval CI], 0.77–1.01) and 0.82 (95% CI, 0.71–0.94), respectively. After 5 years the probability of recurrence in patients with PC‐IgM levels in the highest tertile (> 19.6 RLU/100 ms) was 13.0% (95% CI, 8.1–17.6%), compared with 21.1% (95% CI, 14.9–26.9%) in the middle tertile and 20.6% (95% CI, 14.7–26.0%) in the lowest tertile. The corresponding HR was 0.56 (0.39–0.82) for PC‐IgM levels in the highest compared with the lowest tertile. Neither immunoglobulin G IgG antibody levels to OxLDL nor those to PC were associated with risk of VTE. Conclusion Levels of natural IgM antibodies to oxidation‐specific epitopes are inversely related to the risk of VTE. |
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| Keywords: | immunoglobulin M innate immunity OxLDL phosphocholine venous thrombosis |
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