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- Title
Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis.
- Authors
Disanto, Giulio; Barro, Christian; Benkert, Pascal; Naegelin, Yvonne; Schädelin, Sabine; Giardiello, Antonella; Zecca, Chiara; Blennow, Kaj; Zetterberg, Henrik; Leppert, David; Kappos, Ludwig; Gobbi, Claudio; Kuhle, Jens; Lorscheider, Johannes; Yaldizli, Özgür; Derfuss, Tobias; Achtnichts, Lutz; Nedeltchev, Krassen; Kamm, Christian P; Salmen, Anke
- Abstract
<bold>Objective: </bold>Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS).<bold>Methods: </bold>sNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow-up = 3.1 years, interquartile range [IQR] = 2.0-4.0). We assessed their relation to concurrent clinical, imaging, and treatment parameters and to future clinical outcomes.<bold>Results: </bold>sNfL levels were higher in both MS cohorts than in HC (p < 0.001). We found a strong association between CSF NfL and sNfL (β = 0.589, p < 0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2-65.3) or both brain and spinal gadolinium-enhancing lesions (62.5pg/ml, IQR = 42.7-71.4) had higher sNfL than those without (29.6pg/ml, IQR = 20.9-41.8; β = 1.461, p = 0.005 and β = 1.902, p = 0.002, respectively). sNfL was independently associated with Expanded Disability Status Scale (EDSS) assessments (β = 1.105, p < 0.001) and presence of relapses (β = 1.430, p < 0.001). sNfL levels were lower under disease-modifying treatment (β = 0.818, p = 0.003). Patients with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC-based percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio = 1.94, 95% confidence interval [CI] = 1.21-3.10, p = 0.006) and EDSS worsening (97.5th percentile: OR = 2.41, 95% CI = 1.07-5.42, p = 0.034).<bold>Interpretation: </bold>These results support the value of sNfL as a sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann Neurol 2017;81:857-870.
- Subjects
MULTIPLE sclerosis; BIOMARKERS; CEREBROSPINAL fluid; SERUM; CYTOPLASMIC filaments; BIOLOGICAL assay; BRAIN; COMPARATIVE studies; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; NERVE tissue proteins; RESEARCH; SPINAL cord; DISEASE relapse; PILOT projects; EVALUATION research; CROSS-sectional method
- Publication
Annals of Neurology, 2017, Vol 81, Issue 6, p857
- ISSN
0364-5134
- Publication type
journal article
- DOI
10.1002/ana.24954