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Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa

Kuhle, Jens ; Barro, Christian ; Andreasson, Ulf ; Derfuss, Tobias ; Lindberg, Raija ; Sandelius, Åsa ; Liman, Victor ; Norgren, Niklas ; Blennow, Kaj ; Zetterberg, Henrik

In: Clinical Chemistry and Laboratory Medicine (CCLM), 2016, vol. 54, no. 10, p. 1655-1661

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    Title
    • Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa
    Author
    • Kuhle, Jens. Neurology, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland
    • Barro, Christian. Neurology, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland
    • Andreasson, Ulf. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
    • Derfuss, Tobias. Neurology, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland
    • Lindberg, Raija. Neurology, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland
    • Sandelius, Åsa. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
    • Liman, Victor. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
    • Norgren, Niklas. UmanDiagnostics, Umeå, Sweden
    • Blennow, Kaj. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
    • Zetterberg, Henrik. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Clinical Chemistry and Laboratory Medicine (CCLM), 2016, vol. 54, no. 10, p. 1655-1661. De Gruyter
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:325799
    Summary
    AbstractBackground: Neuronal damage is the morphological substrate of persisting neurological disability. Neurofilaments (Nf) are specific cytoskeletal proteins of neurons and their quantification has shown encouraging results as a biomarker for axonal injury. Methods: We aimed at comparing a widely used conventional ELISA for Nf light chain (NfL) with an electrochemiluminescence-based method (ECL assay) and a newly developed single-molecule array (Simoa) method in clinically relevant cerebrospinal fluid (CSF) and serum samples. Results: Analytical sensitivity was 0.62 pg/mL for Simoa, 15.6 pg/mL for the ECL assay, and 78.0 pg/mL for the ELISA. Correlations between paired CSF and serum samples were strongest for Simoa (r=0.88, p<0.001) and the ECL assay (r=0.78, p<0.001) and weaker for ELISA measurements (r=0.38, p=0.030). CSF NfL measurements between the platforms were highly correlated (r=1.0, p<0.001). Serum NfL levels were highly related between ECL assay and Simoa (r=0.86, p<0.001), and this was less visible between ELISA-ECL assay (r=0.41, p=0.018) and ELISA-Simoa (r=0.43, p=0.013). Multiple sclerosis (MS) patients had significantly higher serum NfL levels than controls when measured with Simoa (p=0.001) but not with the other platforms. Conclusions: We found Simoa to be more sensitive than ELISA or the ECL assay. Our results support the feasibility of quantifying NfL in serum; the results correlate with the more-established CSF NfL test. The highly sensitive Simoa technology deserves further studies in larger patient cohorts to clarify whether serum NfL could be used in the future to measure disease severity and determine prognosis or response to treatment interventions in neurological diseases.