Chitinase 3-like 1: Prognostic biomarker in clinically isolated syndromes

Ester Canto, Mar Tintore, Luisa M. Villar, Carme Costa, Ramil Nurtdinov, José C. Alvarez-Cermeno, Georgina Arrambide, Ferran Reverter, Florian Deisenhammer, Harald Hegen, Mohsen Khademi, Tomas Olsson, Hayrettin Tumani, Eulalia Rodriguez-Martin, Fredrik Piehl, Ales Bartos, Denisa Zimova, Jolana Kotoucova, Jens Kuhle, Ludwig KapposJuan Antonio Garcia-Merino, Antonio José Sánchez, Albert Saiz, Yolanda Blanco, Rogier Hintzen, Naghmeh Jafari, David Brassat, Florian Lauda, Romy Roesler, Konrad Rejdak, Ewa Papuc, Clara De Andrés, Stefan Rauch, Michael Khalil, Christian Enzinger, Daniela Galimberti, Elio Scarpini, Charlotte Teunissen, Alex Sánchez, Alex Rovira, Xavier Montalban, Manuel Comabella

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)918-931
Number of pages14
JournalBrain
Volume138
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Chitinases
Biomarkers
Multiple Sclerosis
Cerebrospinal Fluid
Syndrome
Magnetic Resonance Imaging
Oligoclonal Bands
Proportional Hazards Models
Longitudinal Studies
Cohort Studies
Enzyme-Linked Immunosorbent Assay
Regression Analysis

Keywords

  • biomarker
  • clinically isolated syndrome
  • disability progression
  • multiple sclerosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)
  • Medicine(all)

Cite this

Canto, E., Tintore, M., Villar, L. M., Costa, C., Nurtdinov, R., Alvarez-Cermeno, J. C., ... Comabella, M. (2015). Chitinase 3-like 1: Prognostic biomarker in clinically isolated syndromes. Brain, 138(4), 918-931. https://doi.org/10.1093/brain/awv017

Chitinase 3-like 1 : Prognostic biomarker in clinically isolated syndromes. / Canto, Ester; Tintore, Mar; Villar, Luisa M.; Costa, Carme; Nurtdinov, Ramil; Alvarez-Cermeno, José C.; Arrambide, Georgina; Reverter, Ferran; Deisenhammer, Florian; Hegen, Harald; Khademi, Mohsen; Olsson, Tomas; Tumani, Hayrettin; Rodriguez-Martin, Eulalia; Piehl, Fredrik; Bartos, Ales; Zimova, Denisa; Kotoucova, Jolana; Kuhle, Jens; Kappos, Ludwig; Garcia-Merino, Juan Antonio; Sánchez, Antonio José; Saiz, Albert; Blanco, Yolanda; Hintzen, Rogier; Jafari, Naghmeh; Brassat, David; Lauda, Florian; Roesler, Romy; Rejdak, Konrad; Papuc, Ewa; De Andrés, Clara; Rauch, Stefan; Khalil, Michael; Enzinger, Christian; Galimberti, Daniela; Scarpini, Elio; Teunissen, Charlotte; Sánchez, Alex; Rovira, Alex; Montalban, Xavier; Comabella, Manuel.

In: Brain, Vol. 138, No. 4, 01.04.2015, p. 918-931.

Research output: Contribution to journalArticle

Canto, E, Tintore, M, Villar, LM, Costa, C, Nurtdinov, R, Alvarez-Cermeno, JC, Arrambide, G, Reverter, F, Deisenhammer, F, Hegen, H, Khademi, M, Olsson, T, Tumani, H, Rodriguez-Martin, E, Piehl, F, Bartos, A, Zimova, D, Kotoucova, J, Kuhle, J, Kappos, L, Garcia-Merino, JA, Sánchez, AJ, Saiz, A, Blanco, Y, Hintzen, R, Jafari, N, Brassat, D, Lauda, F, Roesler, R, Rejdak, K, Papuc, E, De Andrés, C, Rauch, S, Khalil, M, Enzinger, C, Galimberti, D, Scarpini, E, Teunissen, C, Sánchez, A, Rovira, A, Montalban, X & Comabella, M 2015, 'Chitinase 3-like 1: Prognostic biomarker in clinically isolated syndromes', Brain, vol. 138, no. 4, pp. 918-931. https://doi.org/10.1093/brain/awv017
Canto E, Tintore M, Villar LM, Costa C, Nurtdinov R, Alvarez-Cermeno JC et al. Chitinase 3-like 1: Prognostic biomarker in clinically isolated syndromes. Brain. 2015 Apr 1;138(4):918-931. https://doi.org/10.1093/brain/awv017
Canto, Ester ; Tintore, Mar ; Villar, Luisa M. ; Costa, Carme ; Nurtdinov, Ramil ; Alvarez-Cermeno, José C. ; Arrambide, Georgina ; Reverter, Ferran ; Deisenhammer, Florian ; Hegen, Harald ; Khademi, Mohsen ; Olsson, Tomas ; Tumani, Hayrettin ; Rodriguez-Martin, Eulalia ; Piehl, Fredrik ; Bartos, Ales ; Zimova, Denisa ; Kotoucova, Jolana ; Kuhle, Jens ; Kappos, Ludwig ; Garcia-Merino, Juan Antonio ; Sánchez, Antonio José ; Saiz, Albert ; Blanco, Yolanda ; Hintzen, Rogier ; Jafari, Naghmeh ; Brassat, David ; Lauda, Florian ; Roesler, Romy ; Rejdak, Konrad ; Papuc, Ewa ; De Andrés, Clara ; Rauch, Stefan ; Khalil, Michael ; Enzinger, Christian ; Galimberti, Daniela ; Scarpini, Elio ; Teunissen, Charlotte ; Sánchez, Alex ; Rovira, Alex ; Montalban, Xavier ; Comabella, Manuel. / Chitinase 3-like 1 : Prognostic biomarker in clinically isolated syndromes. In: Brain. 2015 ; Vol. 138, No. 4. pp. 918-931.
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AU - Canto, Ester

AU - Tintore, Mar

AU - Villar, Luisa M.

AU - Costa, Carme

AU - Nurtdinov, Ramil

AU - Alvarez-Cermeno, José C.

AU - Arrambide, Georgina

AU - Reverter, Ferran

AU - Deisenhammer, Florian

AU - Hegen, Harald

AU - Khademi, Mohsen

AU - Olsson, Tomas

AU - Tumani, Hayrettin

AU - Rodriguez-Martin, Eulalia

AU - Piehl, Fredrik

AU - Bartos, Ales

AU - Zimova, Denisa

AU - Kotoucova, Jolana

AU - Kuhle, Jens

AU - Kappos, Ludwig

AU - Garcia-Merino, Juan Antonio

AU - Sánchez, Antonio José

AU - Saiz, Albert

AU - Blanco, Yolanda

AU - Hintzen, Rogier

AU - Jafari, Naghmeh

AU - Brassat, David

AU - Lauda, Florian

AU - Roesler, Romy

AU - Rejdak, Konrad

AU - Papuc, Ewa

AU - De Andrés, Clara

AU - Rauch, Stefan

AU - Khalil, Michael

AU - Enzinger, Christian

AU - Galimberti, Daniela

AU - Scarpini, Elio

AU - Teunissen, Charlotte

AU - Sánchez, Alex

AU - Rovira, Alex

AU - Montalban, Xavier

AU - Comabella, Manuel

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N2 - 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.

AB - 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.

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