Natural antibodies to oxidation-specific epitopes: innate immune response and venous thromboembolic disease

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.