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Diagnosis of ischemic stroke using circulating levels of brain-specific proteins measured via high-sensitivity digital ELISA

机译:使用高灵敏度数字ELISA测量的脑特异性蛋白质循环水平诊断缺血性脑卒中

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Limited lower detection ranges associated with traditional immunoassay techniques have prevented the use of brain-specific proteins as blood biomarkers of stroke in the acute phase of care, as these proteins are often only present in circulation at low concentrations. Digital ELISA is a newly developed technique with allows for quantification of proteins in biofluids with up to 1000 times greater sensitivity than conventional ELISA techniques. The purpose of this study was to determine whether the extended lower limits of detection associated with digital ELISA could enable the use of brain-specific proteins as blood biomarkers of ischemic stroke during triage. Blood was sampled from ischemic stroke patients (n = 14) at emergency department admission, as well as from neurologically normal controls matched in terms of risk factors for cardiovascular disease (n = 33). Plasma levels of two brain-specific axonal proteins, neurofilament light chain (NfL) and tau, were measured via digital ELISA, and receiver-operating characteristic analysis was used to determine their ability to discriminate between groups. Plasma levels of NfL and tau were both significantly elevated in stroke patients versus controls, and could respectively discriminate between groups with 92.9% sensitivity / 84.9% specificity, and 85.7% sensitivity / 54.6% specificity. Furthermore, adjustment of measured NfL and Tau levels according to the lower-limits of detection associated with commercially-available conventional ELISA assays resulted in a dramatic and statistically significant decrease in diagnostic performance. Collectively, our results suggest that the increased analytical sensitivity of digital ELISA could enable the use of brain-specific proteins as blood biomarkers of ischemic stroke during triage.
机译:与传统免疫测定技术相关的有限检测范围阻止使用脑特异性蛋白质作为急性阶段的中风的血液生物标志物,因为这些蛋白质通常仅存在于低浓度下的循环中。数字ELISA是一种新开发的技术,允许在生物流体中定量蛋白质,比常规ELISA技术更高的灵敏度越大。本研究的目的是确定与数字ELISA相关的延长的检测限延长,可以使脑特异性蛋白质作为缺血性脑卒中过程中的血液生物标志物。在急诊部入院的缺血性脑卒中患者(N = 14)中取样血液,以及在心血管疾病的危险因素方面的神经学常规对照(n = 33)。通过数字ELISA测量两种脑特异性轴突蛋白,神经膜轻链(NFL)和TAU的血浆水平,并且使用接收器操作特性分析来确定其区分组之间的能力。中风患者与对照的血浆和TAU的血浆水平显着升高,并且可以分别在敏感度为92.9%/ 84.9%的群体之间区分,敏感度为85.7%/ 54.6%。此外,根据与商业上可用的常规ELISA测定相关的检测的下限调节测量的NFL和TAU水平导致诊断性能的显着和统计学显着降低。统称,我们的结果表明,数字ELISA的分析敏感性增加可以使脑特异性蛋白质作为缺血性卒中的血液生物标志物。

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