title: Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis.
abstract: 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.
authors: Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Lenka
authors: L
authors: Novakova
authors: Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Markus
authors: M
authors: Axelsson
authors: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors: Mohsen
authors: M
authors: Khademi
authors: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors: Henrik
authors: H
authors: Zetterberg
authors: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Kaj
authors: K
authors: Blennow
authors: Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Clas
authors: C
authors: Malmeström
authors: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors: Fredrik
authors: F
authors: Piehl
authors: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors: Tomas
authors: T
authors: Olsson
authors: Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Jan
authors: J
authors: Lycke
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D054382:Chemokine CXCL13 / Q000134:cerebrospinal fluid; D018450:Disease Progression; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000188:drug therapy*; D000069442:Natalizumab / Q000627:therapeutic use*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D005904:Glial Fibrillary Acidic Protein; D007155:Immunologic Factors; D000069442:Natalizumab; D016900:Neurofilament Proteins; C044882:neurofilament protein L
keywords: biomarkers; cerebrospinal fluid; disease activity; multiple sclerosis; treatment efficacy