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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Lippincott Williams & Wilkins
2021
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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 |
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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 |
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