Jens Kuhle1, Christian Barro2, Giulio Disanto3, Amandine Mathias4, Charlotte Soneson5, Guillaume Bonnier6, Özguer Yaldizli2, Axel Regeniter7, Tobias Derfuss2, Mathieu Canales4, Myriam Schluep8, Renaud Du Pasquier9, Gunnar Krueger10, Cristina Granziera6. 1. Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital of Basel, Basel, Switzerland jens.kuhle@usb.ch. 2. Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital of Basel, Basel, Switzerland. 3. Neurocenter of Southern Switzerland, Ospedale Civico, Lugano, Switzerland. 4. Laboratory of Neuroimmunology, Center of Research in Neurosciences, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland. 5. Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland/University of Zurich, Zurich, Switzerland. 6. 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. 7. Clinical Neurochemistry, University Hospital of Basel, Basel, Switzerland. 8. Service of Neurology, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland. 9. 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. 10. Advanced Clinical Imaging Technology Group, Siemens Healthcare IM BM PI, Lausanne, Switzerland/Healthcare Sector IM&WS S, Siemens Schweiz AG, Renens, Switzerland.
Abstract
BACKGROUND/ OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND/ OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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: Oliver Preische; Stephanie A Schultz; Anja Apel; Jens Kuhle; Stephan A Kaeser; Christian Barro; Susanne Gräber; Elke Kuder-Buletta; Christian LaFougere; Christoph Laske; Jonathan Vöglein; Johannes Levin; Colin L Masters; Ralph Martins; Peter R Schofield; Martin N Rossor; Neill R Graff-Radford; Stephen Salloway; Bernardino Ghetti; John M Ringman; James M Noble; Jasmeer Chhatwal; Alison M Goate; Tammie L S Benzinger; John C Morris; Randall J Bateman; Guoqiao Wang; Anne M Fagan; Eric M McDade; Brian A Gordon; Mathias Jucker Journal: Nat Med Date: 2019-01-21 Impact factor: 53.440
Authors: Arie R Gafson; Nicolas R Barthélemy; Pascale Bomont; Roxana O Carare; Heather D Durham; Jean-Pierre Julien; Jens Kuhle; David Leppert; Ralph A Nixon; Roy O Weller; Henrik Zetterberg; Paul M Matthews Journal: Brain Date: 2020-07-01 Impact factor: 13.501