血浆GFAP免疫测定的验证和年龄相关参考值的建立:连接分析性能和常规实施。

IF 3.7 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY
Burak Arslan, Ulf Andreasson, Elzbieta Rembeza, Markus Axelsson, Lenka Novakova, Bjørn-Eivind Kirsebom, Tormod Fladby, Anna Dittrich, Silke Kern, Ingmar Skoog, Kaj Blennow, Henrik Zetterberg, Hlin Kvartsberg
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引用次数: 0

摘要

目的:胶质纤维酸性蛋白(GFAP)是一种公认的与神经退行性疾病、神经炎性疾病和创伤性脑损伤相关的星形胶质细胞激活的生物标志物。随着人们对基于血液的生物标志物的兴趣日益增加,对分析验证的分析方法和可靠的参考区间的需求对于常规临床实施至关重要。本研究旨在分析验证MSD S-Plex®血浆GFAP免疫测定,并在表面健康人群中建立年龄分层参考区间。方法:本研究分为两期进行。首先,根据临床和实验室标准协会(CLSI)和公布的协议指南评估关键分析验证参数——包括重复性、中间精度、测量范围、干扰和样品稳定性。其次,采用右侧非参数百分位数法,从579名17-91岁的明显健康个体中获得参考区间。计算三个预定义年龄组的年龄特异性上限,并应用连续年龄相关百分位数模型。结果:MSD S-Plex®GFAP分析具有较强的分析性能,重复性变异系数和中间精密度低于12% %。在考虑1:2稀释比后,验证的测量范围为0.425-1760 ng/L,所有校准残差保持在±15 %范围内。GFAP浓度不受溶血影响(p=0.85),在4 °C和冷冻储存条件下保持稳定长达7天。血浆GFAP的年龄分层参考上限为38 pg/mL(18)。结论:本研究证明了MSD S-Plex®GFAP检测的可靠分析性能,并建立了与年龄相关的血浆GFAP参考值。这些发现支持了其常规临床应用的适用性,并增强了其在生物标志物支持的临床算法中对中枢神经系统(CNS)病理(如神经退行性疾病、神经炎性疾病和急性脑损伤)的诊断和监测的适用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Validation of a plasma GFAP immunoassay and establishment of age-related reference values: bridging analytical performance and routine implementation.

Objectives: Glial fibrillary acidic protein (GFAP) is a well-established biomarker of astrocytic activation associated with neurodegenerative diseases, neuroinflammatory disorders, and traumatic brain injury. With increasing interest in blood-based biomarkers, the need for analytically validated assays and reliable reference intervals is critical for routine clinical implementation. This study aimed to analytically validate the MSD S-Plex® GFAP immunoassay for plasma and to establish age-stratified reference intervals in an apparently healthy population.

Methods: This study was conducted in two phases. First, key analytical validation parameters - including repeatability, intermediate precision, measurement range, interferences, and sample stability - were evaluated following Clinical and Laboratory Standards Institute (CLSI) and published protocol guidelines. Second, reference intervals were derived from 579 apparently healthy individuals aged 17-91 years using a right-sided non-parametric percentile method. Age-specific upper reference limits were calculated for three predefined age groups, and a continuous age-dependent centile model was applied.

Results: MSD S-Plex® GFAP assay demonstrated strong analytical performance, with coefficients of variation for repeatability and intermediate precision below 12 %. After accounting for the 1:2 dilution ratio, the validated measurement range was 0.425-1760 ng/L, with all calibration residuals remaining within ±15 %. GFAP concentrations were unaffected by hemolysis (p=0.85) and remained stable for up to 7 days at 4 °C and under frozen storage conditions. Age-stratified upper reference limits for plasma GFAP were established as 38 pg/mL (18-<50 years), 73 pg/mL (≥50-<70 years), and 156 pg/mL (≥70 years). Additionally, sex-related differences were observed after age 50, with females showing higher absolute GFAP levels than males. A strong positive correlation between age and plasma GFAP levels was observed (Spearman's r=0.832, p<0.0001).

Conclusions: This study demonstrates the robust analytical performance of the MSD S-Plex® GFAP assay and establishes age-related reference values for plasma GFAP. These findings support its suitability for routine clinical use and enhance its applicability in the diagnosis and monitoring of central nervous system (CNS) pathologies, such as neurodegenerative diseases, neuroinflammatory disorders, and acute brain injuries, within biomarker-supported clinical algorithms.

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来源期刊
Clinical chemistry and laboratory medicine
Clinical chemistry and laboratory medicine 医学-医学实验技术
CiteScore
11.30
自引率
16.20%
发文量
306
审稿时长
3 months
期刊介绍: Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor over 3. CCLM is issued monthly, and it is published in print and electronically. CCLM is the official journal of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and publishes regularly EFLM recommendations and news. CCLM is the official journal of the National Societies from Austria (ÖGLMKC); Belgium (RBSLM); Germany (DGKL); Hungary (MLDT); Ireland (ACBI); Italy (SIBioC); Portugal (SPML); and Slovenia (SZKK); and it is affiliated to AACB (Australia) and SFBC (France). Topics: - clinical biochemistry - clinical genomics and molecular biology - clinical haematology and coagulation - clinical immunology and autoimmunity - clinical microbiology - drug monitoring and analysis - evaluation of diagnostic biomarkers - disease-oriented topics (cardiovascular disease, cancer diagnostics, diabetes) - new reagents, instrumentation and technologies - new methodologies - reference materials and methods - reference values and decision limits - quality and safety in laboratory medicine - translational laboratory medicine - clinical metrology Follow @cclm_degruyter on Twitter!
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