Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis.
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), α-sAPP and β-sAPP; and Aβ38, Aβ40 and Aβ42, 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.
Joan XXIII University Hospital, Universitat Rovira i Virgili, Tarragona, Spain/Bellvitge University Hospital, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain amane.hj23.ics@gencat.cat.
M Alba Mañé
MA
Martínez
Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Bob
B
Olsson
Bellvitge University Hospital, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Laura
L
Bau
Bellvitge University Hospital, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Elisabet
E
Matas
Bellvitge University Hospital, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Álvaro
Á
Cobo Calvo
Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Ulf
U
Andreasson
Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Kaj
K
Blennow
Bellvitge University Hospital, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Lucia
L
Romero-Pinel
Bellvitge University Hospital, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Sergio
S
Martínez-Yélamos
Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden/Institute of Neurology, University College London, UK.
Henrik
H
Zetterberg
D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000175:diagnosis; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011379:Prognosis; D012008:Recurrence
D015415:Biomarkers
Biomarkers; cerebrospinal fluid; chitinase 3-like 1 protein; diagnostics; disability progression; glial fibrillary acidic protein; multiple sclerosis; neurofilament light protein; prognostic markers