O'Connell Grant C, Alder Megan L, Smothers Christine G, Still Carolyn H, Webel Allison R, Moore Shirley M
Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA.
Neurol Res. 2020 Apr;42(4):346-353. doi: 10.1080/01616412.2020.1726588. Epub 2020 Feb 12.
: Historically, limited sensitivity associated with traditional immunoassay methods has prevented the use of brain-specific proteins as blood biomarkers of traumatic brain injury (TBI) during triage, as these proteins exhibit low circulating concentrations. Digital ELISA is a newly-developed technique that is up to 1000 times more sensitive than conventional ELISA methods. The purpose of this study was to determine whether the use of digital ELISA over conventional ELISA improves the performance of brain-specific proteins as blood biomarkers of TBI during triage.: Blood was sampled from TBI patients (n = 13) at emergency department admission, as well as from neurologically normal controls (n = 72). Serum levels of two brain-specific proteins, neurofilament light chain (NfL) and Tau, were measured via digital ELISA. Estimated conventional ELISA measures were generated by adjusting values according to the lower limits of detection achievable with commercially available conventional ELISA assays, and receiver operating characteristic (ROC) analysis was used to compare the diagnostic performance of digital ELISA measures to estimated conventional ELISA measures in terms of their ability to discriminate between TBI patients and controls.: Used in combination, digital ELISA measures of NfL and Tau could discriminate between groups with 100% sensitivity and 91.7% specificity. Estimated conventional ELISA measures could only discriminate between groups with 7.7% sensitivity and 94.4% specificity. This difference in diagnostic performance was statistically significant when comparing areas under ROC curves.: The use of digital ELISA over conventional ELISA methods improves the diagnostic performance of circulating brain-specific proteins for detection of TBI during triage.
从历史上看，传统免疫测定方法的灵敏度有限，这使得脑特异性蛋白无法在分诊期间用作创伤性脑损伤（TBI）的血液生物标志物，因为这些蛋白在循环中的浓度较低。数字酶联免疫吸附测定（Digital ELISA）是一种新开发的技术，其灵敏度比传统酶联免疫吸附测定方法高出多达1000倍。本研究的目的是确定在分诊期间，使用数字酶联免疫吸附测定法而非传统酶联免疫吸附测定法是否能提高脑特异性蛋白作为TBI血液生物标志物的性能。
在急诊科收治时，从TBI患者（n = 13）以及神经功能正常的对照者（n = 72）中采集血液。通过数字酶联免疫吸附测定法测量两种脑特异性蛋白神经丝轻链（NfL）和Tau的血清水平。根据市售传统酶联免疫吸附测定法可达到的检测下限调整数值，生成估计的传统酶联免疫吸附测定测量值，并使用受试者操作特征（ROC）分析来比较数字酶联免疫吸附测定测量值与估计的传统酶联免疫吸附测定测量值在区分TBI患者和对照者方面的诊断性能。
联合使用时，NfL和Tau的数字酶联免疫吸附测定测量值能够以100%的灵敏度和91.7%的特异性区分不同组。估计的传统酶联免疫吸附测定测量值只能以7.7%的灵敏度和94.4%的特异性区分不同组。比较ROC曲线下面积时，这种诊断性能的差异具有统计学意义。
在分诊期间，使用数字酶联免疫吸附测定法而非传统酶联免疫吸附测定法可提高循环脑特异性蛋白检测TBI的诊断性能。
