First Department of Propaedeutic Internal Medicine, Joint Rheumatology Program, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Rheumatology (Oxford). 2021 Apr 6;60(4):1669-1675. doi: 10.1093/rheumatology/keaa548.
Amyloid-beta1-40 (Aβ40) is a pro-inflammatory peptide under investigation as a novel biomarker of vascular inflammation, endothelial dysfunction and atherothrombosis in the general population. Herein we tested the hypothesis that Aβ40 is deregulated in APS, a systemic autoimmune disease characterized by a thrombo-inflammatory state.
Between January 2016 and July 2017, we consecutively recruited 80 regularly followed thrombotic APS patients (44 primary, 36 SLE/APS) and 80 age- and sex-matched controls. Plasma Aβ40 levels were measured using ELISA and APS-related clinical and laboratory characteristics were recorded. The adjusted Global Anti-Phospholipid Syndrome Score (aGAPSS), a validated risk score in APS, was calculated as a comparator to Aβ40 performance to detect arterial thrombotic APS-related events.
Higher Aβ40 levels were significantly associated with the presence of APS [odds ratio (OR) 1.024 per 1 pg/ml (95% CI 1.007, 1.041)] after adjustment for cardiovascular risk factors (CVRFs), including smoking, arterial hypertension, dyslipidaemia and BMI, and for estimated glomerular filtration rate (eGFR). Among APS patients, increased high-sensitivity CRP (hs-CRP) serum levels was the only independent determinant of Aβ40 levels. Importantly, Aβ40 levels above the optimal receiver operating characteristics (ROC)-derived cut-off value were independently associated with recurrent arterial events [OR 4.93 (95% CI 1.31, 18.51)] after adjustment for age, sex, CVRFs, hs-CRP and high anti-β2 glycoprotein I IgG titres. Finally, by ROC curve analysis, Aβ40 provided incremental additive value over the aGAPSS by significantly improving its discrimination ability for recurrent arterial thromboses.
In APS, Aβ40 plasma levels are elevated and associated with an adverse thrombo-inflammatory profile. The pathophysiological and prognostic role of Aβ40 in APS merits further investigation.
β淀粉样蛋白 1-40（Aβ40）是一种促炎肽，目前正在作为一种新的血管炎症、内皮功能障碍和动脉粥样硬化的生物标志物在普通人群中进行研究。在此，我们检验了以下假说，即在以血栓炎症状态为特征的系统性自身免疫性疾病抗磷脂综合征（APS）中，Aβ40 是失调的。
2016 年 1 月至 2017 年 7 月，我们连续招募了 80 例经常接受治疗的血栓性 APS 患者（44 例原发性，36 例 SLE/APS）和 80 名年龄和性别匹配的对照者。使用 ELISA 法测量血浆 Aβ40 水平，并记录 APS 相关的临床和实验室特征。计算了经过验证的 APS 风险评分——调整后的全球抗磷脂综合征评分（aGAPSS），作为与 Aβ40 检测动脉血栓性 APS 相关事件的性能比较。
经过心血管危险因素（CVRFs），包括吸烟、动脉高血压、血脂异常和 BMI，以及估算肾小球滤过率（eGFR）的调整后，较高的 Aβ40 水平与 APS 的存在显著相关[每增加 1pg/ml 的比值比（OR）为 1.024（95%CI 为 1.007，1.041）]。在 APS 患者中，hs-CRP 血清水平升高是 Aβ40 水平的唯一独立决定因素。重要的是，根据最佳受试者工作特征（ROC）衍生的截止值，Aβ40 水平高于此值与复发性动脉事件独立相关[比值比（OR）为 4.93（95%CI 为 1.31，18.51）]，调整因素包括年龄、性别、CVRFs、hs-CRP 和高抗-β2 糖蛋白 I IgG 滴度。最后，通过 ROC 曲线分析，Aβ40 提供了增量附加价值，通过显著提高其对复发性动脉血栓形成的鉴别能力，从而改善了 aGAPSS 的鉴别能力。
在 APS 中，Aβ40 血浆水平升高并与不良的血栓炎症谱相关。Aβ40 在 APS 中的病理生理和预后作用值得进一步研究。
