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

• Published in: Journal of neurochemistry Vol. 141; no. 2; pp. 296 - 304
• Main Authors: Novakova, Lenka, Axelsson, Markus, Khademi, Mohsen, Zetterberg, Henrik, Blennow, Kaj, Malmeström, Clas, Piehl, Fredrik, Olsson, Tomas, Lycke, Jan
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2017
• Subjects: Adolescent; Adult; Biomarkers; Biomarkers - cerebrospinal fluid; cerebrospinal fluid; Chemokine CXCL13 - cerebrospinal fluid; disease activity; Disease Progression; Drug therapy; Female; Glial Fibrillary Acidic Protein - cerebrospinal fluid; Humans; Immunologic Factors - therapeutic use; Male; Medicin och hälsovetenskap; Middle Aged; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - cerebrospinal fluid; Multiple Sclerosis, Relapsing-Remitting - diagnosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Natalizumab - therapeutic use; Neurochemistry; Neurofilament Proteins - cerebrospinal fluid; Neurosciences; Neurovetenskaper; treatment efficacy; Treatment Outcome; Young Adult; disease activity; biomarkers; multiple sclerosis; cerebrospinal fluid; treatment efficacy
• ISSN: 0022-3042; 1471-4159; 1471-4159
• DOI: 10.1111/jnc.13881

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. CSF biomarkers reflect different aspects of the pathophysiology of multiple sclerosis. The present study investigated the influence of interferon beta and natalizumab on seven biomarkers and their correlation with clinical and radiological outcomes. The results indicate that CSF levels of neurofilament light protein (NFL), C‐X‐C motif chemokine 13 (CXCL13), chitinase‐3‐like protein 1 (CHI3L1), and chitotriosidase (CHIT1) correlate with the clinical and/or radiological disease activity, providing additional dimensions in the assessment of treatment efficacy.