Cargando…

CSF Chitinase 3–Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis

OBJECTIVE: This study aimed to identify long-term prognostic protein biomarkers associated with disease progression in patients with progressive multiple sclerosis (MS). METHODS: CSF samples were collected from a discovery cohort of 28 patients with progressive MS who participated in a clinical tria...

Descripción completa

Detalles Bibliográficos
Autores principales: Comabella, Manuel, Sastre-Garriga, Jaume, Borras, Eva, Villar, Luisa M., Saiz, Albert, Martínez-Yélamos, Sergio, García-Merino, Juan Antonio, Pinteac, Rucsanda, Fissolo, Nicolas, Sánchez López, Antonio J., Costa-Frossard, Lucienne, Blanco, Yolanda, Llufriu, Sara, Vidal-Jordana, Angela, Sabidó, Eduard, Montalban, Xavier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428018/
https://www.ncbi.nlm.nih.gov/pubmed/34497102
http://dx.doi.org/10.1212/NXI.0000000000001082
_version_ 1783750293650931712
author Comabella, Manuel
Sastre-Garriga, Jaume
Borras, Eva
Villar, Luisa M.
Saiz, Albert
Martínez-Yélamos, Sergio
García-Merino, Juan Antonio
Pinteac, Rucsanda
Fissolo, Nicolas
Sánchez López, Antonio J.
Costa-Frossard, Lucienne
Blanco, Yolanda
Llufriu, Sara
Vidal-Jordana, Angela
Sabidó, Eduard
Montalban, Xavier
author_facet Comabella, Manuel
Sastre-Garriga, Jaume
Borras, Eva
Villar, Luisa M.
Saiz, Albert
Martínez-Yélamos, Sergio
García-Merino, Juan Antonio
Pinteac, Rucsanda
Fissolo, Nicolas
Sánchez López, Antonio J.
Costa-Frossard, Lucienne
Blanco, Yolanda
Llufriu, Sara
Vidal-Jordana, Angela
Sabidó, Eduard
Montalban, Xavier
author_sort Comabella, Manuel
collection PubMed
description OBJECTIVE: This study aimed to identify long-term prognostic protein biomarkers associated with disease progression in patients with progressive multiple sclerosis (MS). METHODS: CSF samples were collected from a discovery cohort of 28 patients with progressive MS who participated in a clinical trial with interferon beta. Patients were classified into high and low disability progression phenotypes according to numeric progression rates (NPR) and step-based progression rates (SPR) after a mean follow-up time of 12 years. Protein abundance was measured by shotgun proteomics. Selected proteins from the discovery cohort were quantified by parallel reaction monitoring in CSF samples from an independent validation cohort of 41 patients with progressive MS classified also into high and low disability progression phenotypes after a mean follow-up time of 7 years. RESULTS: Of 2,548 CSF proteins identified in the discovery cohort, 10 were selected for validation based on their association with long-term disability progression: SPATS2-like protein, chitinase 3–like 2 (CHI3L2), plasma serine protease inhibitor, metallothionein-3, phospholipase D4, beta-hexosaminidase, neurexophilin-1, adipocyte enhancer-binding protein 1, cathepsin L1, and lipopolysaccharide-binding protein. Only CHI3L2 was validated, and patients with high disability progression exhibited significantly higher CSF protein levels compared with patients with low disability progression (p = 0.03 for NPR and p = 0.02 for SPR). CHI3L2 levels showed good performance to discriminate between high and low disability progression in patients with progressive MS (area under the curve 0.73; sensitivity 90% and specificity 63%). CONCLUSIONS: Although further confirmatory studies are needed, we propose CSF CHI3L2 as a prognostic protein biomarker associated with long-term disability progression in patients with progressive MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that high CSF CHI3L2 levels identified higher disability progression in patients with progressive MS.
format Online
Article
Text
id pubmed-8428018
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Lippincott Williams & Wilkins
record_format MEDLINE/PubMed
spelling pubmed-84280182021-09-10 CSF Chitinase 3–Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis Comabella, Manuel Sastre-Garriga, Jaume Borras, Eva Villar, Luisa M. Saiz, Albert Martínez-Yélamos, Sergio García-Merino, Juan Antonio Pinteac, Rucsanda Fissolo, Nicolas Sánchez López, Antonio J. Costa-Frossard, Lucienne Blanco, Yolanda Llufriu, Sara Vidal-Jordana, Angela Sabidó, Eduard Montalban, Xavier Neurol Neuroimmunol Neuroinflamm Article OBJECTIVE: This study aimed to identify long-term prognostic protein biomarkers associated with disease progression in patients with progressive multiple sclerosis (MS). METHODS: CSF samples were collected from a discovery cohort of 28 patients with progressive MS who participated in a clinical trial with interferon beta. Patients were classified into high and low disability progression phenotypes according to numeric progression rates (NPR) and step-based progression rates (SPR) after a mean follow-up time of 12 years. Protein abundance was measured by shotgun proteomics. Selected proteins from the discovery cohort were quantified by parallel reaction monitoring in CSF samples from an independent validation cohort of 41 patients with progressive MS classified also into high and low disability progression phenotypes after a mean follow-up time of 7 years. RESULTS: Of 2,548 CSF proteins identified in the discovery cohort, 10 were selected for validation based on their association with long-term disability progression: SPATS2-like protein, chitinase 3–like 2 (CHI3L2), plasma serine protease inhibitor, metallothionein-3, phospholipase D4, beta-hexosaminidase, neurexophilin-1, adipocyte enhancer-binding protein 1, cathepsin L1, and lipopolysaccharide-binding protein. Only CHI3L2 was validated, and patients with high disability progression exhibited significantly higher CSF protein levels compared with patients with low disability progression (p = 0.03 for NPR and p = 0.02 for SPR). CHI3L2 levels showed good performance to discriminate between high and low disability progression in patients with progressive MS (area under the curve 0.73; sensitivity 90% and specificity 63%). CONCLUSIONS: Although further confirmatory studies are needed, we propose CSF CHI3L2 as a prognostic protein biomarker associated with long-term disability progression in patients with progressive MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that high CSF CHI3L2 levels identified higher disability progression in patients with progressive MS. Lippincott Williams & Wilkins 2021-09-08 /pmc/articles/PMC8428018/ /pubmed/34497102 http://dx.doi.org/10.1212/NXI.0000000000001082 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Comabella, Manuel
Sastre-Garriga, Jaume
Borras, Eva
Villar, Luisa M.
Saiz, Albert
Martínez-Yélamos, Sergio
García-Merino, Juan Antonio
Pinteac, Rucsanda
Fissolo, Nicolas
Sánchez López, Antonio J.
Costa-Frossard, Lucienne
Blanco, Yolanda
Llufriu, Sara
Vidal-Jordana, Angela
Sabidó, Eduard
Montalban, Xavier
CSF Chitinase 3–Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis
title CSF Chitinase 3–Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis
title_full CSF Chitinase 3–Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis
title_fullStr CSF Chitinase 3–Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis
title_full_unstemmed CSF Chitinase 3–Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis
title_short CSF Chitinase 3–Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis
title_sort csf chitinase 3–like 2 is associated with long-term disability progression in patients with progressive multiple sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428018/
https://www.ncbi.nlm.nih.gov/pubmed/34497102
http://dx.doi.org/10.1212/NXI.0000000000001082
work_keys_str_mv AT comabellamanuel csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT sastregarrigajaume csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT borraseva csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT villarluisam csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT saizalbert csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT martinezyelamossergio csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT garciamerinojuanantonio csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT pinteacrucsanda csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT fissolonicolas csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT sanchezlopezantonioj csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT costafrossardlucienne csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT blancoyolanda csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT llufriusara csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT vidaljordanaangela csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT sabidoeduard csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis
AT montalbanxavier csfchitinase3like2isassociatedwithlongtermdisabilityprogressioninpatientswithprogressivemultiplesclerosis