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Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis

Giulio Disanto, Christian Barro, Pascal Benkert, Yvonne Naegelin, Sabine Schädelin, Antonella Giardiello, Chiara Zecca, Kaj Blennow, Henrik Zetterberg, David Leppert, Ludwig Kappos, Claudio Gobbi, Jens Kuhle & Swiss Multiple Sclerosis Cohort Study Group

abstract

OBJECTIVE
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).

METHODS
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.

RESULTS
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).

INTERPRETATION
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.
   
citation Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A, Zecca C, Blennow K, Zetterberg H, Leppert D, Kappos L, Gobbi C, Kuhle J, Swiss Multiple Sclerosis Cohort Study Group . Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol 2017; 81:857-870.
   
type journal paper/review (English)
date of publishing 6-2017
journal title Ann Neurol (81/6)
ISSN electronic 1531-8249
pages 857-870
PubMed 28512753
DOI 10.1002/ana.24954