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Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis.

Journal article
Authors Lenka Nováková Nyrén
Markus Axelsson
Mohsen Khademi
Henrik Zetterberg
Kaj Blennow
Clas Malmeström
Fredrik Piehl
Tomas Olsson
Jan Lycke
Published in Journal of neurochemistry
Volume 141
Issue 2
Pages 296–304
ISSN 1471-4159
Publication year 2017
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Pages 296–304
Language en
Subject categories Neurochemistry


Cerebrospinal fluid (CSF) biomarkers can reflect different aspects of the pathophysiology of relapsing-remitting multiple sclerosis (RRMS). Understanding the impact of different disease modifying therapies on the CSF biomarker profile may increase their implementation in clinical practice and their appropriateness for monitoring treatment efficacy. This study investigated the influence of first-line (interferon beta) and second-line (natalizumab) therapies on seven CSF biomarkers in RRMS and their correlation with clinical and radiological outcomes. We included 59 RRMS patients and 39 healthy controls. The concentrations of C-X-C motif chemokine 13 (CXCL13), C-C motif chemokine ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein, neurofilament light protein (NFL), and neurogranin were determined by ELISA, and chitotriosidase (CHIT1) was analyzed by spectrofluorometry. RRMS patients had higher levels of NFL, CXCL13, CHI3L1, and CHIT1 than controls (p < 0.001). Subgroup analysis revealed higher NFL, CXCL13 and CHIT1 levels in patients treated with first-line therapy compared to second-line therapy (p = 0.008, p = 0.001 and p = 0.026, respectively). NFL and CHIT1 levels correlated with relapse status, and NFL and CXCL13 levels correlated with the formation of new magnetic resonance imaging lesions. Furthermore, we found an association between inflammatory and degenerative biomarkers. The results indicate that CSF levels of NFL, CXCL13, CHI3L1, and CHIT1 correlate with the clinical and/or radiological disease activity, providing additional dimensions in the assessment of treatment efficacy.

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