Arcaro Marina, Fenoglio Chiara, Serpente Maria, Arighi Andrea, Fumagalli Giorgio G, Sacchi Luca, Floro Stefano, D'Anca Marianna, Sorrentino Federica, Visconte Caterina, Perego Alberto, Scarpini Elio, Galimberti Daniela
Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, 20122 Milan, Italy.
Biomedicines. 2022 Oct 21;10(10):2667. doi: 10.3390/biomedicines10102667.
Recently, a fully automated instrument for the detection of the Cerebrospinal Fluid (CSF) biomarker for Alzheimer’s disease (AD) (low concentration of Amyloid-beta 42 (Aβ42), high concentration of total tau (T-tau) and Phosphorylated-tau (P-tau181)), has been implemented, namely CLEIA. We conducted a comparative analysis between ELISA and CLEIA methods in order to evaluate the analytical precision and the diagnostic performance of the novel CLEIA system on 111 CSF samples. Results confirmed a robust correlation between ELISA and CLEIA methods, with an improvement of the accuracy with the new CLEIA methodology in the detection of the single biomarkers and in their ratio values. For Aβ42 regression analysis with Passing−Bablok showed a Pearson correlation coefficient r = 0.867 (0.8120; 0.907% 95% CI p < 0.0001), T-tau analysis: r = 0.968 (0.954; 0.978% 95% CI p < 0.0001) and P-tau181: r = 0.946 (0.922; 0.962 5% 95% CI p < 0.0001). The overall ROC AUC comparison between ROC in ELISA and ROC in CLEIA confirmed a more accurate ROC AUC with the new automatic method: T-tau AUC ELISA = 0.94 (95% CI 0.89; 0.99 p < 0.0001) vs. AUC CLEIA = 0.95 (95% CI 0.89; 1.00 p < 0.0001), and P-tau181 AUC ELISA = 0.91 (95% CI 0.85; 0.98 p < 0.0001) vs. AUC CLEIA = 0.98 (95% CI 0.95; 1.00 p < 0.0001). The performance of the new CLEIA method in automation is comparable and, for tau and P-tau181, even better, as compared with standard ELISA. Hopefully, in the future, automation could be useful in clinical diagnosis and also in the context of clinical studies.
最近，一种用于检测阿尔茨海默病（AD）脑脊液（CSF）生物标志物（低浓度β淀粉样蛋白42（Aβ42）、高浓度总tau蛋白（T-tau）和磷酸化tau蛋白（P-tau181））的全自动仪器已投入使用，即化学发光酶免疫分析（CLEIA）。我们对酶联免疫吸附测定（ELISA）和CLEIA方法进行了对比分析，以评估这种新型CLEIA系统对111份脑脊液样本的分析精密度和诊断性能。结果证实ELISA和CLEIA方法之间存在强相关性，新的CLEIA方法在检测单个生物标志物及其比值时准确性有所提高。对于Aβ42，采用Passing-Bablok回归分析显示皮尔逊相关系数r = 0.867（0.8120；0.907，95%置信区间，p < 0.0001），T-tau分析：r = 0.968（0.954；0.978，95%置信区间，p < 0.0001），P-tau181：r = 0.946（0.922；0.962，95%置信区间，p < 0.0001）。ELISA的ROC曲线下面积（ROC AUC）与CLEIA的ROC AUC总体比较证实，新的自动方法的ROC AUC更准确：T-tau的AUC ELISA = 0.94（95%置信区间0.89；0.99，p < 0.0001），而AUC CLEIA = 0.95（95%置信区间0.89；1.00，p < 0.0001）；P-tau181的AUC ELISA = 0.91（95%置信区间0.85；0.98，p < 0.0001），而AUC CLEIA = 0.98（95%置信区间0.95；1.00，p < 0.0001）。与标准ELISA相比，新的CLEIA方法在自动化方面的性能相当，对于tau和P-tau181甚至更好。有望在未来，自动化在临床诊断以及临床研究背景下都将发挥作用。
