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Diagnosis of ischemic stroke using circulating levels of brain-specific proteins measured via high-sensitivity digital ELISA.
Brain Research ( IF 2.7 ) Pub Date : 2020-04-27 , DOI: 10.1016/j.brainres.2020.146861
Grant C O'Connell 1 , Megan L Alder 1 , Christine G Smothers 1 , Carolyn H Still 1 , Allison R Webel 1 , Shirley M Moore 1
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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.

中文翻译:

使用通过高灵敏度数字 ELISA 测量的脑特异性蛋白质的循环水平诊断缺血性中风。

与传统免疫测定技术相关的有限较低检测范围阻止了将脑特异性蛋白质用作急性护理阶段中风的血液生物标志物,因为这些蛋白质通常仅以低浓度存在于循环中。数字 ELISA 是一种新开发的技术,可以对生物流体中的蛋白质进行定量,其灵敏度比传统 ELISA 技术高出 1000 倍。本研究的目的是确定与数字 ELISA 相关的扩展检测下限是否能够在分类期间使用脑特异性蛋白质作为缺血性中风的血液生物标志物。在急诊科入院时从缺血性中风患者 (n = 14) 中采集血液样本,以及来自在心血管疾病危险因素方面匹配的神经学正常对照(n = 33)。通过数字 ELISA 测量两种大脑特异性轴突蛋白、神经丝轻链 (NfL) 和 tau 的血浆水平,并使用接收器操作特征分析来确定它们区分组的能力。与对照组相比,中风患者的血浆 NfL 和 tau 水平均显着升高,并且可以分别以 92.9% 的敏感性/84.9% 的特异性和 85.7% 的敏感性/54.6% 的特异性区分组。此外,根据与市售常规 ELISA 检测相关的检测下限调整测量的 NfL 和 Tau 水平,导致诊断性能显着下降且具有统计学意义。
更新日期:2020-04-27
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