Nancy University Hospital, Vascular Medicine Division and Regional Competence Center for Rare Vascular and Systemic Autoimmune Diseases, Nancy, France.
Inserm, U1116, Nancy, France.
J Appl Lab Med. 2020 Nov 1;5(6):1242-1252. doi: 10.1093/jalm/jfaa072.
Antibodies binding to domain I of β2-glycoprotein I (aDI) and activated protein C (APC) resistance are associated with an increased risk of thrombosis in cross-sectional studies. The objective of this study was to assess their predictive value for future thromboembolic events in patients with antiphospholipid antibodies (aPL) or antiphospholipid syndrome.
This prospective multicenter cohort study included consecutive patients with aPL or systemic lupus erythematosus. We followed 137 patients (43.5 ± 15.4 year old; 107 women) for a mean duration of 43.1 ± 20.7 months.
We detected aDI IgG antibodies by ELISA in 21 patients. An APC sensitivity ratio (APCsr) was determined using a thrombin generation-based test. The APCsr was higher in patients with anti-domain I antibodies demonstrating APC resistance (0.75 ± 0.13 vs 0.48 ± 0.20, P < 0.0001). In univariate analysis, the hazard ratio (HR) for thrombosis over time was higher in patients with aDI IgG (3.31 [95% CI, 1.15-9.52]; P = 0.03) and patients with higher APC resistance (APCsr >95th percentile; HR, 6.07 [95% CI, 1.69-21.87]; P = 0.006). A sensitivity analysis showed an increased risk of higher aDI IgG levels up to HR 5.61 (95% CI, 1.93-16.31; P = 0.01). In multivariate analysis, aDI IgG (HR, 3.90 [95% CI, 1.33-11.46]; P = 0.01) and APC resistance (HR, 4.98 [95% CI, 1.36-18.28]; P = 0.02) remained significant predictors of thrombosis over time.
Our study shows that novel tests for antibodies recognizing domain I of β2-glycoprotein I and functional tests identifying APC resistance are significant predictors of thrombosis over time and may be useful for risk stratification.
β2-糖蛋白 I 结构域 I（aDI）结合抗体和活化蛋白 C（APC）抵抗与横断面研究中的血栓形成风险增加相关。本研究的目的是评估它们在抗磷脂抗体（aPL）或抗磷脂综合征患者中对未来血栓栓塞事件的预测价值。
这项前瞻性多中心队列研究纳入了连续的 aPL 或系统性红斑狼疮患者。我们对 137 例患者（43.5±15.4 岁；107 名女性）进行了平均 43.1±20.7 个月的随访。
我们通过 ELISA 检测到 21 例患者存在 aDI IgG 抗体。使用基于凝血酶生成的试验测定 APC 敏感性比（APCsr）。对 aDI 抗体表现出 APC 抵抗的患者中，APCsr 更高（0.75±0.13 与 0.48±0.20，P<0.0001）。在单因素分析中，随着时间的推移，存在 aDI IgG 的患者的血栓形成风险比（HR）更高（3.31 [95% CI，1.15-9.52]；P=0.03）和 APC 抵抗更高的患者（APCsr >95 百分位；HR，6.07 [95% CI，1.69-21.87]；P=0.006）。敏感性分析显示，aDI IgG 水平升高的风险增加，HR 为 5.61（95% CI，1.93-16.31；P=0.01）。在多因素分析中，aDI IgG（HR，3.90 [95% CI，1.33-11.46]；P=0.01）和 APC 抵抗（HR，4.98 [95% CI，1.36-18.28]；P=0.02）仍然是随时间发生血栓形成的显著预测因子。
我们的研究表明，识别 β2-糖蛋白 I 结构域 I 的新型抗体检测和鉴定 APC 抵抗的功能检测是随时间发生血栓形成的显著预测因子，可能有助于风险分层。
