Fredrik Piehl1, Ingrid Kockum1, Mohsen Khademi1, Kaj Blennow2, Jan Lycke3, Henrik Zetterberg4, Tomas Olsson1. 1. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden/Department of Neurology, Karolinska University Hospital Solna, Stockholm, Sweden. 2. Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden/Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 3. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 4. Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden/Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden/Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
Abstract
BACKGROUND: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS). OBJECTIVE: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod. METHODS: A first cohort consisted of MS patients ( n = 39) and neurological disease controls ( n = 27) where CSF and plasma/serum had been collected for diagnostic purposes. A second cohort ( n = 243) consisted of patients from a post-marketing study of fingolimod. NFL was determined with Single Molecule Array (Simoa™) technology (detection threshold 1.95 pg/mL). RESULTS: Mean NFL pg/mL (standard deviation ( SD)) was 341 (267) and 1475 (2358) in CSF and 8.2 (3.58) and 17.0 (16.94) in serum from controls and MS, respectively. CSF/serum and plasma/serum levels were highly correlated ( n = 66, rho = 0.672, p < 0.0001 and n = 16, rho = 0.684, p = 0.009, respectively). In patients starting fingolimod ( n = 243), mean NFL pg/mL ( SD) in plasma was reduced between baseline (20.4 (10.7)) and at 12 months (13.5 (7.3), p < 3 × 10-6), and levels remained stable at 24 months (13.2 (6.2)). CONCLUSION: NFL in serum and CSF are highly correlated and plasma NFL levels decrease after switching to highly effective MS therapy. Blood NFL measurement can be considered as a biomarker for MS therapy response.
BACKGROUND: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS). OBJECTIVE: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod. METHODS: A first cohort consisted of MS patients ( n = 39) and neurological disease controls ( n = 27) where CSF and plasma/serum had been collected for diagnostic purposes. A second cohort ( n = 243) consisted of patients from a post-marketing study of fingolimod. NFL was determined with Single Molecule Array (Simoa™) technology (detection threshold 1.95 pg/mL). RESULTS: Mean NFL pg/mL (standard deviation ( SD)) was 341 (267) and 1475 (2358) in CSF and 8.2 (3.58) and 17.0 (16.94) in serum from controls and MS, respectively. CSF/serum and plasma/serum levels were highly correlated ( n = 66, rho = 0.672, p < 0.0001 and n = 16, rho = 0.684, p = 0.009, respectively). In patients starting fingolimod ( n = 243), mean NFL pg/mL ( SD) in plasma was reduced between baseline (20.4 (10.7)) and at 12 months (13.5 (7.3), p < 3 × 10-6), and levels remained stable at 24 months (13.2 (6.2)). CONCLUSION:NFL in serum and CSF are highly correlated and plasma NFL levels decrease after switching to highly effective MS therapy. Blood NFL measurement can be considered as a biomarker for MS therapy response.
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