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Brain. 2015 Apr;138(Pt 4):918-31. doi: 10.1093/brain/awv017. Epub 2015 Feb 13.

Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes.

Author information

1
1 Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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2 Departments of Neurology and Immunology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion sanitaria, Madrid, Spain.
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3 Departament d'Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona.
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4 Department of Clinical Neurology, Innsbruck Medical University, Innsbruck, Austria.
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5 Neuroimmunology Unit Department of Clinical Neuroscience, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden.
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6 Department of Neurology, CSF Laboratory and MS Outpatient Unit, University of Ulm, Germany.
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7 Charles University in Prague, Third Faculty of Medicine and University Hospital Kralovske Vinohrady, Department of Neurology, Šrobárova 50, 100 34 Prague 10, Czech Republic.
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8 Neurology and Clinical Neuroimmunology, University Hospital, University of Basel, Basel, Switzerland.
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9 Neuroimmunology Unit and Neurology Service, Hospital Universitario Puerta de Hierro, Madrid, Spain.
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10 Service of Neurology, Hospital Clínic, Universitat de Barcelona and Institut d́Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
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11 Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
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12 Pole des Neurosciences and UMR 1043, Hôpital Purpan, Université de Toulouse III, Toulouse, France.
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13 Department of Neurology, Medical University of Lublin, Lublin, Poland 14 Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
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13 Department of Neurology, Medical University of Lublin, Lublin, Poland.
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15 Department of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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16 Department of Radiology, Innsbruck Medical University, Innsbruck, Austria.
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17 Department of Neurology, Medical University of Graz, Graz, Austria.
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18 Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
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19 BIoMS-eu Network and Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, VU University Medical Centre, Amsterdam, The Netherlands.
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3 Departament d'Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona 20 Unitat d'Estadística i Bioinformàtica, Institut de Recerca, HUVH, Barcelona, Spain.
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21 Unitat de RM. Servei de Radiologia, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
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1 Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain manuel.comabella@vhir.org.

Abstract

Chitinase 3-like 1 (CHI3L1) has been proposed as a biomarker associated with the conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes, based on the finding of increased cerebrospinal fluid CHI3L1 levels in clinically isolated syndrome patients who later converted to multiple sclerosis compared to those who remained as clinically isolated syndrome. Here, we aimed to validate CHI3L1 as a prognostic biomarker in a large cohort of patients with clinically isolated syndrome. This is a longitudinal cohort study of clinically isolated syndrome patients with clinical, magnetic resonance imaging, and cerebrospinal fluid data prospectively acquired. A total of 813 cerebrospinal fluid samples from patients with clinically isolated syndrome were recruited from 15 European multiple sclerosis centres. Cerebrospinal fluid CHI3L1 levels were measured by enzyme-linked immunosorbent assay. Multivariable Cox regression models were used to investigate the association between cerebrospinal fluid CHI3L1 levels and time to conversion to multiple sclerosis and time to reach Expanded Disability Status Scale 3.0. CHI3L1 levels were higher in patients who converted to clinically definite multiple sclerosis compared to patients who continued as clinically isolated syndrome (P = 8.1 × 10(-11)). In the Cox regression analysis, CHI3L1 levels were a risk factor for conversion to multiple sclerosis (hazard ratio = 1.7; P = 1.1 × 10(-5) using Poser criteria; hazard ratio = 1.6; P = 3.7 × 10(-6) for McDonald criteria) independent of other covariates such as brain magnetic resonance imaging abnormalities and presence of cerebrospinal fluid oligoclonal bands, and were the only significant independent risk factor associated with the development of disability (hazard ratio = 3.8; P = 2.5 × 10(-8)). High CHI3L1 levels were associated with shorter time to multiple sclerosis (P = 3.2 × 10(-9) using Poser criteria; P = 5.6 × 10(-11) for McDonald criteria) and more rapid development of disability (P = 1.8 × 10(-10)). These findings validate cerebrospinal fluid CHI3L1 as a biomarker associated with the conversion to multiple sclerosis and development of disability and reinforce the prognostic role of CHI3L1 in patients with clinically isolated syndrome. We propose that determining cerebrospinal fluid chitinase 3-like 1 levels at the time of a clinically isolated syndrome event will help identify those patients with worse disease prognosis.

KEYWORDS:

biomarker; clinically isolated syndrome; disability progression; multiple sclerosis

PMID:
25688078
DOI:
10.1093/brain/awv017
[Indexed for MEDLINE]

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