Serum GFAP as a biomarker for progression in multiple sclerosis: assay comparison and a large reference database of healthy controls
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Eline A.J. Willemse
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Pascal Benkert
,
Sabine Schaedelin
Abstract
Objectives
Compare Elecsys (Roche) and Simoa (Quanterix) immunoassays for serum glial fibrillary acidic protein (GFAP) using our reference database and Z scores, and evaluate their prognostic value for progression independent of relapse activity (PIRA) in multiple sclerosis (MS).
Methods
Platform correlation was assessed in 612 samples from healthy controls (n=188; median [interquartile range, IQR] age 45.1 [36.4–61.7] years) and people with MS (n=424; 45.3 [35.2–53.9] years). Elecsys values were converted to Z scores via Passing-Bablok-derived regression and validated in fingolimod (n=414), and B-cell depleting therapy (BCDT; n=353) cohorts. Z scores and hazard ratios (HRs) for time-to-PIRA were compared using Cox regression.
Results
GFAPSimoa and GFAPElecsys measurements were correlated (r=0.94), with Elecsys values ∼54 % lower (GFAPElecsys, ng/L=2.847 [95 % confidence interval, CI: 1.335 – 4.98] + 0.457 [0.434 – 0.478] * GFAPSimoa, ng/L). In univariable Cox models, GFAPSimoa and GFAPElecsys Z scores were associated with time-to-PIRA in both validation cohorts. In multivariable Cox models, higher GFAPSimoa Z scores were associated with shorter time-to-PIRA in fingolimod cohort (HR: 1.27 [95 % CI 1.08 – 1.50], p=0.0031) and trended toward significance in BCDT (1.18 [0.99 – 1.41, p=0.0693). In contrast, GFAPElecsys Z scores were associated with time-to-PIRA in both cohorts (fingolimod: 1.27 [1.09 – 1.48], p=0.0023; BCDT: (1.19 [1.00 – 1.40], p=0.0487).
Conclusions
Serum GFAP measured by Elecsys shows a comparable association with time-to-PIRA as Simoa, and GFAPSimoa Z scores can be successfully bridged to GFAPElecsys Z scores, supporting Elecsys`s potential for clinical implementation.
Funding source: Merck
Funding source: Sanofi
Funding source: Novartis
Funding source: The Swiss MS Society
Funding source: Roche
Funding source: Celgene
Funding source: Biogen
Acknowledgments
We express our deep thankfulness to patients and relatives for their participation and support, study nurses in participating centers for their motivated collaboration and recruitment efforts, and the administrative personnel of the SMSC.
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Research ethics: This cohort study, conducted since January 1, 2012, followed the Declaration of Helsinki and was approved by the Ethics Committees of all participating centers.
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Informed consent: Written informed consent was obtained from all HCs and pwMS.
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Author contributions: Significant contribution to: conception and design of the study (E.A.J.W., S.Sa., P.B., S.Sc., A.M.M., J.O., N.G., D.L., M.E., and J.K.), acquisition and analysis of data (E.A.J.W., S.Sa., P.B., S.Sc., A.M.M, J.O., N.G., K.B., M.Herm., S.M., S.F., J.F.V.G., A.Z., G.D., M.D., C.G., C.P.K., C.P., C.Z., P.H.L., R.H., M.Herw., C.G., D.L., M.E. and J.K.), participation in drafting a significant portion of the manuscript or figures (E.A.J.W., S.Sa., P.B., S.Sc., and J.K.). All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: E.A.J.W. is a contractor for Roche Diagnostics as of November 1, 2025. S.Sa. has received compensation for lectures from Novartis and Merck, has served on scientific advisory boards for Merck and Sanofi; and has received grants from the Swedish Foundation for MS Research; NEURO Sweden; the Edit Jacobson Foundation; the Rune and Ulla Amlövs Foundation for Neurological Research; the Göran Jahnsons Foundation; the Gothenburg Foundation for Neurological Research; the Gothenburg Medical Society; the Family Bursies Foundation; the Swedish Society of Medicine (SLS-1019901); the Swedish Federal Government [LUA/ALF agreement, 2025-MC-001011]; the Sparbank Foundation in Varberg; the Scientific Council Region Halland; and an unconditional grant from Sanofi (2025-MC-001011; this funder had no role in study design, data collection, analysis, or interpretation). P.B., S.Sc., A.M.M. report no disclosure. J.O. her employer (University hospital Basel) received research support by the Swiss MS Society, Roche and Novartis. N.G., K.B., M.Herm. report no disclosure. S.M. received honoraria for travel, honoraria for lectures/consulting, and/or grants for studies from Almirall, Biogen, Celgene, Novartis, Teva, Merck Serono, Genzyme, Roche, and Bayer Schweiz. S.F. has received honoraria for lectures and advisory boards as well as research and travel support from Biogen, Novartis, Almirall, Bayer Schweiz AG, Teva, Merck, Sanofi Genzyme, Roche and the Swiss MS Society. J.F.V.G., A.Z. report no disclosure. G.D. received financial support from Teva, Merck Serono, Biogen Idec, Bayer Schering, Genzyme, Roche, and Novartis. The submitted work is not related to any of these agreements. C.Z. received financial support from Teva, Merck Serono, Biogen Idec, Bayer Schering, Genzyme, Roche, and Novartis. The submitted work is not related to any of these agreements. M.D. is CEO of Neurostatus-UHB Ltd. He has received travel support from Bayer AG, Biogen, Teva Pharmaceuticals and Sanofi Genzyme and research support from the University Hospital Basel. C.G. reports that the Ente Ospedaliero Cantonale (employer) received compensation for speaking activities, consulting fees, or research grants from Almirall, Biogen Idec, Bristol Meyer Squibb, Lundbeck, Merck, Novartis, Sanofi, Teva Pharma, Roche. C.P. her institution received financial support and honoraria from Merck Serono, Biogen, Roche and Novartis none related to this work. C.Z. her institution the Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland receives financial support from Teva, Merck Serono, Biogen, Genzyme, Roche, Celgene, Bayer and Novartis. P.H.L. received honoraria for speaking and or travel expense from Biogen, Merck, Novartis, Roche; consulting fees from Biogen, GeNeuro, Merck, Novartis, Roche; research support from Biogen, Merck, Novartis. None were related to this work. R.H. received speaker/advisor honorary from Merck, Novartis, Roche, Biogen, Alexion, Sanofi, Janssen, Bristol-Myers Squibb, Teva/Mepha and Almirall. He received research support within the last 5 years from Roche, Merck, Sanofi, Biogen, Chiesi, and Bristol-Myers Squibb. He also received research grants from the Swiss MS Society, the SITEM Insel Support Fund and is a member of the Advisory Board of the Swiss and International MS Society. He also serves as deputy editor in chief for Journal of Central Nervous System disease and is part of the ECTRIMS Young Investigator Committee. M.Herw. reports no disclosure. C.G. his instutition the Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland received financial support from Teva, Merck Serono, Biogen, Genzyme, Roche, Celgene, Bayer and Novartis. D.L. was Chief Medical Officer of GeNeuro until end of 2023; he is a consultant for Rewind Therapeutics. M.E. has received travel support from Roche. J.K. received speaker fees, research support, travel support, and/or served on advisory boards by Swiss MS Society, Swiss National Research Foundation (320030_212534/1), United Kingdom Dementia Research Institute, University of Basel, Progressive MS Alliance, Alnylam, Bayer, Biogen, Bristol Myers Squibb, Celgene, Immunic, Merck, Neurogenesis, Novartis, Octave Bioscience, Quanterix, Roche, Sanofi, Stata DX.
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Research funding: The SMSC study received funding from the Swiss MS Society and grant funding from Biogen, Celgene, Merck, Novartis, Roche, and Sanofi. The funders of the study had no role in study design, data collection, analysis, and interpretation, writing or approval of this report for publication.
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Data availability: Written requests for access to the data reported in this paper will be considered by the corresponding author and a decision made about the appropriateness of the use of the data. If the use is appropriate, a data sharing agreement will be put in place before a fully de-identified version of the dataset used for the analysis with individual participant data is made available. The internet-based application for determination of sGFAP Z scores is available at: https://shiny.dkfbasel.ch/baselgfapreference/.
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2025-1480).
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