Center for Stroke Research Berlin (CSB) Charité - Universitätsmedizin Berlin Berlin Germany.
Department of Neurology at Evangelical Hospital Oldenburg Carl von Ossietzky University Oldenburg Germany.
J Am Heart Assoc. 2023 Dec 5;12(23):e032441. doi: 10.1161/JAHA.123.032441. Epub 2023 Nov 28.
Vasoregulatory autoantibodies including autoantibodies targeting G-protein-coupled receptors might play a functional role in vascular diseases. We investigated the impact of vasoregulatory autoantibodies on clinical outcome after ischemic stroke.
Data were used from the PROSCIS-B (Prospective Cohort With Incident Stroke-Berlin). Autoantibody-targeting receptors such as angiotensin II type 1 receptor (AT1R), endothelin-1 type A receptor, complement factor-3 and -5 receptors, vascular endothelial growth factor receptor-1 and -2, vascular endothelial growth factor A and factor B were measured. We explored associations of high antibody levels with (1) poor functional outcome defined as modified Rankin Scale >2 or Barthel Index <60 at 1 year after stroke, (2) Barthel Index scores over time using general estimating equations, and (3) secondary vascular events (recurrent stroke, myocardial infarction) or death up to 3 years using Cox proportional hazard models. We included 491 patients with ischemic stroke with data on autoantibody levels and outcome. In models adjusted for demographics and vascular risk factors, high autoantibody concentrations (quartile 4) targeting complement factor C3a receptor, vascular endothelial growth factor receptor-2, and vascular endothelial growth factor B were associated with poor functional outcome at 1 year: (odds ratio, 2.0 [95% CI, 1.1-3.6]; odds ratio, 1.8 [95% CI, 1.1-3.2]; and odds ratio, 2.1 [95% CI, 1.2-3.6], respectively) and with lower Barthel Index scores over 3 years (complement factor C3a receptor: adjusted β=-3.3 [95% CI, -5.7 to -0.5]; VEGF-B: adjusted β=-2.4 [95% CI, -4.8 to -0.06]). Patients with high autoantibody levels were not at higher risk for secondary vascular events or death.
High levels of autoantibodies against vascular endothelial growth factor receptor-2, vascular endothelial growth factor B, and complement factor C3a receptor measured are associated with poor functional outcome after stroke but not with recurrent vascular events or death.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT01363856.
血管调节自身抗体，包括靶向 G 蛋白偶联受体的自身抗体，可能在血管疾病中发挥功能作用。我们研究了血管调节自身抗体对缺血性脑卒中后临床结局的影响。
本研究数据来自 PROSCIS-B（前瞻性卒中合并事件-柏林）。测量了自身抗体靶向的受体，如血管紧张素 II 型 1 受体（AT1R）、内皮素-1 型 A 受体、补体因子 3 和 5 受体、血管内皮生长因子受体-1 和 -2、血管内皮生长因子 A 和因子 B。我们探讨了高抗体水平与以下因素的相关性：（1）1 年后改良 Rankin 量表>2 分或 Barthel 指数<60 分的不良功能结局，（2）使用一般估计方程的 Barthel 指数评分随时间的变化，以及（3）使用 Cox 比例风险模型的复发性卒中、心肌梗死或 3 年内死亡等次要血管事件。我们纳入了 491 例缺血性卒中患者，这些患者有自身抗体水平和结局的数据。在调整了人口统计学和血管危险因素的模型中，补体因子 C3a 受体、血管内皮生长因子受体-2 和血管内皮生长因子 B 靶向的高自身抗体浓度（四分位 4）与 1 年后的不良功能结局相关：（比值比，2.0[95%可信区间，1.1-3.6]；比值比，1.8[95%可信区间，1.1-3.2]；和比值比，2.1[95%可信区间，1.2-3.6]），并且在 3 年内 Barthel 指数评分较低（补体因子 C3a 受体：调整后的β值=-3.3[95%可信区间，-5.7 至-0.5]；VEGF-B：调整后的β值=-2.4[95%可信区间，-4.8 至-0.06]）。高自身抗体水平的患者发生继发性血管事件或死亡的风险没有增加。
测量的血管内皮生长因子受体-2、血管内皮生长因子 B 和补体因子 C3a 受体的高自身抗体水平与卒中后的不良功能结局相关，但与复发性血管事件或死亡无关。
