Method comparison of plasma and CSF GFAP immunoassays across multiple platforms.

IF 3.7 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY
Burak Arslan, Elzbieta Rembeza, Sofia Rasch, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Hlin Kvartsberg
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引用次数: 0

Abstract

Objectives: Glial fibrillary acidic protein (GFAP) is a biomarker of astrocytic activation associated with neurodegenerative diseases, neuroinflammatory disorders, and traumatic brain injury. However, the lack of standardized methods for quantifying GFAP across different immunoassay platforms poses challenges for its clinical implementation. This study aimed to compare the analytical performance of multiple commercially available and in-house immunoassays for GFAP quantification in plasma and cerebrospinal fluid (CSF) to assess their agreement and potential interchangeability.

Methods: We conducted a method comparison using four plasma GFAP immunoassays (Simoa, Ella, Alinity, and MSD) and four CSF GFAP assays (ELISA, Ella, Alinity and MSD). Anonymized leftover plasma and CSF samples were analyzed across platforms. Sample sizes for the pairwise comparisons ranged from 23 to 52 for plasma and 34 to 51 for CSF. Pairwise comparisons were performed using Spearman correlation, Bland-Altman analysis, and Passing-Bablok regression to assess systematic and proportional biases. Outliers were identified and excluded to ensure robust statistical evaluation.

Results: Strong correlations were observed across all platforms (Spearman's r=0.827-0.927 for plasma; r=0.937-0.958 for CSF). However, significant systematic and proportional biases were present in several comparisons, preventing direct interchangeability of results. In plasma, Simoa consistently reported higher GFAP concentrations compared with Ella and Alinity, while Alinity overestimated levels relative to Ella. Similarly, in CSF, ELISA tended to underestimate GFAP concentrations compared with Alinity, MSD, and Ella, with the largest discrepancy observed between ELISA and MSD.

Conclusions: Despite strong correlations, substantial method-dependent biases indicate that GFAP measurements across different immunoassay platforms need to be standardized to ensure harmonization and reliable clinical application of GFAP as a biomarker.

多平台血浆和脑脊液GFAP免疫测定方法比较。
目的:胶质原纤维酸性蛋白(GFAP)是与神经退行性疾病、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。然而,缺乏跨不同免疫分析平台量化GFAP的标准化方法,这对其临床实施构成了挑战。本研究旨在比较多种市售和内部用于血浆和脑脊液(CSF) GFAP定量的免疫测定方法的分析性能,以评估它们的一致性和潜在的互换性。方法:采用四种血浆GFAP免疫测定法(Simoa、Ella、Alinity和MSD)和四种CSF GFAP测定法(ELISA、Ella、Alinity和MSD)进行方法比较。跨平台分析匿名剩余血浆和脑脊液样本。两两比较的样本量为血浆23 - 52,脑脊液34 - 51。两两比较采用Spearman相关、Bland-Altman分析和Passing-Bablok回归来评估系统偏差和比例偏差。识别和排除异常值以确保可靠的统计评估。结果:在所有平台中均观察到强相关性(血浆的Spearman r=0.827-0.927,脑脊液的r=0.937-0.958)。然而,在一些比较中存在显著的系统和比例偏差,阻止了结果的直接互换性。在血浆中,Simoa报告的GFAP浓度始终高于Ella和Alinity,而Alinity则高估了相对于Ella的水平。同样,在CSF中,与Alinity、MSD和Ella相比,ELISA倾向于低估GFAP浓度,ELISA和MSD之间的差异最大。结论:尽管有很强的相关性,但大量的方法依赖偏差表明,不同免疫分析平台之间的GFAP测量需要标准化,以确保GFAP作为生物标志物的协调和可靠的临床应用。
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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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