Burak Arslan, Elzbieta Rembeza, Sofia Rasch, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Hlin Kvartsberg
{"title":"多平台血浆和脑脊液GFAP免疫测定方法比较。","authors":"Burak Arslan, Elzbieta Rembeza, Sofia Rasch, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Hlin Kvartsberg","doi":"10.1515/cclm-2025-0667","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Method comparison of plasma and CSF GFAP immunoassays across multiple platforms.\",\"authors\":\"Burak Arslan, Elzbieta Rembeza, Sofia Rasch, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Hlin Kvartsberg\",\"doi\":\"10.1515/cclm-2025-0667\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":10390,\"journal\":{\"name\":\"Clinical chemistry and laboratory medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical chemistry and laboratory medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1515/cclm-2025-0667\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical chemistry and laboratory medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1515/cclm-2025-0667","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
Method comparison of plasma and CSF GFAP immunoassays across multiple platforms.
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.
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
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