Journal
MULTIPLE SCLEROSIS JOURNAL
Volume 21, Issue 5, Pages 550-561Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458514549397
Keywords
Biomarkers; cerebrospinal fluid; chitinase 3-like 1 protein; diagnostics; disability progression; glial fibrillary acidic protein; multiple sclerosis; neurofilament light protein; prognostic markers
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Funding
- Fundacio Hospital Universitari de Tarragona Joan XXIII
- Fundacio Institut d'Investigacio Biomedica de Bellvitge (IDIBELL)
- Biogen Idec
- Teva Pharmaceutical Industries
- Sanofi-Aventis
- Merck Serono
- Novartis
- Bayer Schering Pharma
- Teva
- Bayer Schering pharmaceuticals
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Objective: To investigate glial and neuronal biomarkers in cerebrospinal fluid (CSF) samples from patients with relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS), and to evaluate their ability to predict conversion from CIS to clinically definite MS (CDMS) and also disability progression in MS. Methods: CSF levels of neurofilament light protein (NFL), t-tau, p-tau, glial fibrillary acidic protein (GFAP), S-100B, human chitinase 3-like 1 protein (YKL-40), monocyte chemoattractant protein-1 (MCP-1), -sAPP and -sAPP; and A38, A40 and A42, were analyzed in 109 CIS patients and 192 RRMS patients. The mean follow-up time of these 301 patients was 11.7 6.4 years. Results: High levels of NFL were associated with early conversion from CIS to CDMS (hazard ratio (HR) with 95% confidence interval (CI): 2.69 (1.75 - 4.15); p < 0.0001). High levels of YKL-40 and GFAP were associated with earlier progression in the Expanded Disability Status Scale (EDSS), score 3: YKL-40 (HR (95% CI): 2.78 (1.48 - 5.23); p = 0.001) and GFAP (HR (95% CI): 1.83 (1.01 - 3.35); p = 0.04). High levels of YKL-40 were associated with earlier progression to EDSS 6 (HR (95% CI): 4.57 (1.01 - 20.83); p = 0.05). Conclusions: CSF levels of NFL in CIS patients are an independent prognostic marker for conversion to CDMS. Whereas, CSF levels of YKL-40 and GFAP are independent prognostic markers for disability progression in MS.
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