title: Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity.
abstract: Neurofilament light chain (NfL) levels in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients correlate with the degree of neuronal injury. To date, little is known about NfL concentrations in the serum of relapsing remitting multiple sclerosis (RRMS) patients and their relationship with CSF levels and magnetic resonance imaging (MRI) measures of disease severity. We aimed to validate the quantification of NfL in serum samples of RRMS, as a biofluid source easily accessible for longitudinal studies.
  
  
  
  A total of 31 RRMS patients underwent CSF and serum sampling. After a median time of 3.6 years, 19 of these RRMS patients, 10 newly recruited RRMS patients and 18 healthy controls had a 3T MRI and serum sampling. NfL concentrations were determined by electrochemiluminescence immunoassay.
  
  
  
  NfL levels in serum were highly correlated to levels in CSF (r = 0.62, p = 0.0002). Concentrations in serum were higher in patients than in controls at baseline (p = 0.004) and follow-up (p = 0.0009) and did not change over time (p = 0.56). Serum NfL levels correlated with white matter (WM) lesion volume (r = 0.68, p < 0.0001), mean T1 (r = 0.40, p = 0.034) and T2* relaxation time (r = 0.49, p = 0.007) and with magnetization transfer ratio in normal appearing WM (r = -0.41, p = 0.029).
  
  
  
  CSF and serum NfL levels were highly correlated, and serum concentrations were increased in RRMS. Serum NfL levels correlated with MRI markers of WM disease severity. Our findings further support longitudinal studies of serum NfL as a potential biomarker of on-going disease progression and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.
authors.affiliation: Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital of Basel, Basel, Switzerland jens.kuhle@usb.ch.
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhle
authors.affiliation: Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital of Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Barro
authors.affiliation: Neurocenter of Southern Switzerland, Ospedale Civico, Lugano, Switzerland.
authors.forename: Giulio
authors.initials: G
authors.lastname: Disanto
authors.affiliation: Laboratory of Neuroimmunology, Center of Research in Neurosciences, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Amandine
authors.initials: A
authors.lastname: Mathias
authors.affiliation: Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland/University of Zurich, Zurich, Switzerland.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Soneson
authors.affiliation: Advanced Clinical Imaging Technology Group, Siemens Healthcare IM BM PI, Lausanne, Switzerland/Neuro-Immunology, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland/LTS5, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bonnier
authors.affiliation: Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital of Basel, Basel, Switzerland.
authors.forename: Özguer
authors.initials: Ö
authors.lastname: Yaldizli
authors.affiliation: Clinical Neurochemistry, University Hospital of Basel, Basel, Switzerland.
authors.forename: Axel
authors.initials: A
authors.lastname: Regeniter
authors.affiliation: Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital of Basel, Basel, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Derfuss
authors.affiliation: Laboratory of Neuroimmunology, Center of Research in Neurosciences, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Canales
authors.affiliation: Service of Neurology, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Myriam
authors.initials: M
authors.lastname: Schluep
authors.affiliation: Laboratory of Neuroimmunology, Center of Research in Neurosciences, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland/Service of Neurology, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Renaud
authors.initials: R
authors.lastname: Du Pasquier
authors.affiliation: Advanced Clinical Imaging Technology Group, Siemens Healthcare IM BM PI, Lausanne, Switzerland/Healthcare Sector IM&WS S, Siemens Schweiz AG, Renens, Switzerland.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Krueger
authors.affiliation: Advanced Clinical Imaging Technology Group, Siemens Healthcare IM BM PI, Lausanne, Switzerland/Neuro-Immunology, Neurology Division, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland/LTS5, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Granziera
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000473:pathology*; D016900:Neurofilament Proteins / Q000097:blood*; D012720:Severity of Illness Index; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D055815:Young Adult
chemical_list: D016900:Neurofilament Proteins; C044882:neurofilament protein L
keywords: Neurofilament light chain (NfL); magnetization transfer ratio (MTR); relaxometry; serum; white matter lesions