Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Karl Landsteiner Institute for Clinical Thrombosis Research, Vienna, Austria.
J Thromb Haemost. 2018 Jan;16(1):31-35. doi: 10.1111/jth.13874. Epub 2017 Nov 8.
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.
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.
天然针对氧化特异性表位的抗体具有抗血栓形成特性。我们评估了自然 IgM 和 IgG 抗体与静脉血栓形成风险之间的关系。低自然 IgM 抗体水平的患者发生复发性血栓的风险更高。高 IgM 水平的保护作用表明先天免疫反应在血栓形成中的作用。
天然针对氧化低密度脂蛋白 (OxLDL) 和磷酸胆碱 (PC) 的抗体可预防动脉粥样硬化血栓形成事件。先天免疫机制是否与静脉血栓栓塞症 (VTE) 的发病机制相关尚不清楚。
我们通过酶联免疫吸附试验测量了 663 例无诱因 VTE 患者血浆中氧化型低密度脂蛋白 (OxLDL) 和 PC 的免疫球蛋白 M (IgM) 抗体水平。这些患者在停止抗凝治疗后中位随访 8.8 年。研究终点为复发性 VTE。
与发生复发性 VTE 的患者 (n = 174，26.2%) 相比，无复发 VTE 的患者的 OxLDL-IgM 和 PC-IgM 抗体水平更高。OxLDL-IgM 或 PC-IgM 每增加一倍，复发的风险比 (HR) 分别为 0.88 (95%置信区间 [CI]，0.77-1.01) 和 0.82 (95% CI，0.71-0.94)。在 PC-IgM 水平处于最高三分位数 (> 19.6 RLU/100 ms) 的患者中，5 年后的复发率为 13.0% (95% CI，8.1-17.6%)，而在中间三分位数和最低三分位数患者中，复发率分别为 21.1% (95% CI，14.9-26.9%) 和 20.6% (95% CI，14.7-26.0%)。与最低三分位数相比，PC-IgM 水平最高的患者 HR 为 0.56 (0.39-0.82)。OxLDL 天然 IgG 抗体水平和 PC 天然 IgG 抗体水平与 VTE 风险均无关联。
针对氧化特异性表位的天然 IgM 抗体水平与 VTE 风险呈负相关。
