Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes
Open accessAbstract
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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The five biomarkers were selected based on their role in myeloid activation and their potential diagnostic or prognostic value, as indicated in prior research.
“These five biomarkers were selected based on their role in myeloid activation and their potential diagnostic or prognostic value, as indicated in prior research on MS and other neurological disorders10,15–17.”
From CHIT1 at diagnosis predicts faster disability progression and reflects early microglial activation in multiple sclerosis (2024) · cites this paper as [15]
The Results section (page not provided) reports CHI3L1 expression in macrophages, microglia and CSF monocytes; the Discussion identifies CHI3L1 as a prognostic biomarker in clinically isolated syndrome. The paper supports the rationale for CHI3L1, but does not establish that all five biomarkers have those roles or explain the citing authors’ selection of them. (LLM, conf=0.86)
Experimental — accuracy not yet measuredYKL-40 is a secreted glycoprotein that in the CNS is expressed by microglia and astrocytes and is considered one of the most promising biomarkers of neuroinflammation in AD.
“YKL-40 is a secreted glycoprotein that in the CNS is expressed by microglia and astrocytes19,20 and is considered one of the most promising biomarkers of neuroinflammation in AD.”
From CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease (2018) · cites this paper as [19]
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“These fi vebiomarkerswere selected based on their role in myeloid activation and their potential diagnostic or prognostic value, as indicated in prior research on MS and other neurological disorders 10,15 – 17 .”
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- Authors
- Cantó, E., Tintoré, M., Villar, L. M., Costa, C., Nurtdinov, R., Álvarez-Cermeño, J. C., Arrambide, G., Reverter, F., Deisenhammer, F., Hegen, H., Khademi, M., Olsson, T., Tumani, H., Rodríguez-Martín, E., Piehl, F., Bartos, A., Zimova, D., Kotoucova, J., Kuhle, J., Kappos, L., García-Merino, J. A., Sánchez, A. J., 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.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Instituto Ramón y Cajal de Investigación Sanitaria (ES)
- Innsbruck Medical University (AT)
- Karolinska University Hospital (SE)
- Universität Ulm (DE)
- Charles University (CZ)
- University of Basel (CH)
- Hospital Universitario Puerta de Hierro Majadahonda (ES)
- Hospital Clínic de Barcelona (ES)
- Erasmus MC (NL)
- Université Toulouse III - Paul Sabatier (FR)
- Medical University of Lublin (PL)
- Medical University of Graz (AT)
- University of Milan (IT)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- ORCID
- Tintoré, Mar
- Villar, Luisa M.
- Costa, Carme
- Nurtdinov, Ramil
- Arrambide, Georgina
- Deisenhammer, Florian
- Hegen, Harald
- Khademi, Mohsen
- Olsson, Tomas
- Tumani, Hayrettin
- Piehl, Fredrik
- Kotoucova, Jolana
- Kappos, Ludwig
- García-Merino, Juan Antonio
- Sánchez, Antonio José
- Saiz, Albert
- Blanco, Yolanda
- Hintzen, Rogier
- Jafari, Naghmeh
- Brassat, David
- Rejdak, Konrad
- Rauch, Stefan
- Khalil, Michael
- Enzinger, Christian
- Galimberti, Daniela
- Scarpini, Elio
- Teunissen, Charlotte
- Comabella, Manuel
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-02-12
- Volume
- 138
- Issue
- 4
- Pages
- 918-931
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2103879732
- Cited by
- 193
- References
- 54
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 17 · 2023: 19 · 2022: 21 · 2021: 23 · 2020: 24 · 2019: 12 · 2018: 13 · 2017: 15 · 2016: 17 · 2015: 9 · 2013: 1
- FWCI
- 14.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Univerzita Karlova v Praze (PRVOUK P34)
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- YKL-40, clinically isolated syndrome, multiple sclerosis, prognostic factors, conversion to multiple sclerosis, cerebrospinal fluid biomarkers, disability progression, Expanded Disability Status Scale, oligoclonal bands, brain MRI abnormalities, Poser criteria, McDonald criteria
- MeSH terms
- Chitinase-3-Like Protein 1, Adult, Aged, Aged, 80 and over, Brain, Demyelinating Diseases, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Biomarkers, Lectins, Adipokines, Young Adult
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