Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple Sclerosis
Background: Neurofilament light chain protein (NFL) and chitinase3-like1 (CHI3L1) have gained importance recently as prognostic biomarkers in multiple sclerosis (MS).Objectives: We aimed to investigate NFL and CHI3L1 cerebrospinal fluid (CSF) profiles in multiple sclerosis and the informative and pr...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2019.01008/full |
| _version_ | 1828895575363289088 |
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| author | Sara Gil-Perotin Sara Gil-Perotin Jessica Castillo-Villalba Jessica Castillo-Villalba Laura Cubas-Nuñez Laura Cubas-Nuñez Raquel Gasque David Hervas Josep Gomez-Mateu Carmen Alcala Francisco Perez-Miralles Francisco Gascon Jose Andres Dominguez Bonaventura Casanova Bonaventura Casanova |
| author_facet | Sara Gil-Perotin Sara Gil-Perotin Jessica Castillo-Villalba Jessica Castillo-Villalba Laura Cubas-Nuñez Laura Cubas-Nuñez Raquel Gasque David Hervas Josep Gomez-Mateu Carmen Alcala Francisco Perez-Miralles Francisco Gascon Jose Andres Dominguez Bonaventura Casanova Bonaventura Casanova |
| author_sort | Sara Gil-Perotin |
| collection | DOAJ |
| description | Background: Neurofilament light chain protein (NFL) and chitinase3-like1 (CHI3L1) have gained importance recently as prognostic biomarkers in multiple sclerosis (MS).Objectives: We aimed to investigate NFL and CHI3L1 cerebrospinal fluid (CSF) profiles in multiple sclerosis and the informative and prognostic potential of the individual and combined measures.Methods: CSF NFL and CHI3L1 levels were measured in a cross-sectional cohort of 157 MS patients [99 relapsing-remitting (RRMS), 35 secondary progressive (SPMS), and 23 primary progressive (PPMS)]. Clinical relapse and/or gadolinium-enhanced lesions (GEL) in MRI within 90 days from CSF collection by lumbar puncture (LP) were registered and considered as indicators of disease activity. Longitudinal treatment and disability data were evaluated during medical visits with a median follow-up of 50 months.Results: CSF levels of NFL and CHI3L1 were higher in MS patients compared to non-MS controls. In RRMS and SPMS patients, increased NFL levels were associated with clinical relapse, and gadolinium-enhanced lesions in MRI (p < 0.001), while high CHI3L1 levels were characteristic of progressive disease (p = 0.01). In RRMS patients, CSF NFL, and CHI3L1 levels correlated with each other (r = 0.58), and with IgM-oligoclonal bands (p = 0.02 and p = 0.004, respectively). In addition, CSF CHI3L1 concentration was a predictor for 1-point EDSS worsening {HR = 2.99 [95% CI (1.27, 7.07)]} and progression during follow-up {HR = 18 [95% CI (2.31, 141.3)]}. The pattern of combined measure of biomarkers was useful to discriminate MS phenotypes and to anticipate clinical progression: RRMS more frequently presented high NFL combined with low CHI3L1 levels, compared to SPMS (HR 0.41 [0.18–0.82]), and PPMS (HR 0.46 [0.19–0.87]), while elevation of both biomarkers preceded diagnosis of clinical progression in RRMS patients (log rank = 0.02).Conclusions: Individual measures of CSF NFL and CHI3L1 are biomarkers of disease activity and progression, respectively. The pattern of combined measure discriminates MS phenotypes. It also predicts the subset of RRMS patients that will progress clinically allowing early intervention. |
| first_indexed | 2024-12-13T14:28:59Z |
| format | Article |
| id | doaj.art-13f821624bc540a8b1285c29b182d2b3 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-13T14:28:59Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj.art-13f821624bc540a8b1285c29b182d2b32022-12-21T23:41:52ZengFrontiers Media S.A.Frontiers in Neurology1664-22952019-09-011010.3389/fneur.2019.01008471572Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple SclerosisSara Gil-Perotin0Sara Gil-Perotin1Jessica Castillo-Villalba2Jessica Castillo-Villalba3Laura Cubas-Nuñez4Laura Cubas-Nuñez5Raquel Gasque6David Hervas7Josep Gomez-Mateu8Carmen Alcala9Francisco Perez-Miralles10Francisco Gascon11Jose Andres Dominguez12Bonaventura Casanova13Bonaventura Casanova14Multiple Sclerosis Unit, Hospital Universitari i Politècnic La Fe, Valencia, SpainResearch Group in Neuroimmunology, Health Research Institute La Fe, Valencia, SpainMultiple Sclerosis Unit, Hospital Universitari i Politècnic La Fe, Valencia, SpainResearch Group in Neuroimmunology, Health Research Institute La Fe, Valencia, SpainMultiple Sclerosis Unit, Hospital Universitari i Politècnic La Fe, Valencia, SpainResearch Group in Neuroimmunology, Health Research Institute La Fe, Valencia, SpainResearch Group in Neuroimmunology, Health Research Institute La Fe, Valencia, SpainBiostatistics Unit, Health Research Institute La Fe, Valencia, SpainNeurology Department, Hospital Universitari Dr. Peset, Valencia, SpainMultiple Sclerosis Unit, Hospital Universitari i Politècnic La Fe, Valencia, SpainMultiple Sclerosis Unit, Hospital Universitari i Politècnic La Fe, Valencia, SpainNeuroimmunology Unit, Hospital Clínic de València, Valencia, SpainNeuroimmunology Unit, Hospital Clínic de València, Valencia, SpainMultiple Sclerosis Unit, Hospital Universitari i Politècnic La Fe, Valencia, SpainResearch Group in Neuroimmunology, Health Research Institute La Fe, Valencia, SpainBackground: Neurofilament light chain protein (NFL) and chitinase3-like1 (CHI3L1) have gained importance recently as prognostic biomarkers in multiple sclerosis (MS).Objectives: We aimed to investigate NFL and CHI3L1 cerebrospinal fluid (CSF) profiles in multiple sclerosis and the informative and prognostic potential of the individual and combined measures.Methods: CSF NFL and CHI3L1 levels were measured in a cross-sectional cohort of 157 MS patients [99 relapsing-remitting (RRMS), 35 secondary progressive (SPMS), and 23 primary progressive (PPMS)]. Clinical relapse and/or gadolinium-enhanced lesions (GEL) in MRI within 90 days from CSF collection by lumbar puncture (LP) were registered and considered as indicators of disease activity. Longitudinal treatment and disability data were evaluated during medical visits with a median follow-up of 50 months.Results: CSF levels of NFL and CHI3L1 were higher in MS patients compared to non-MS controls. In RRMS and SPMS patients, increased NFL levels were associated with clinical relapse, and gadolinium-enhanced lesions in MRI (p < 0.001), while high CHI3L1 levels were characteristic of progressive disease (p = 0.01). In RRMS patients, CSF NFL, and CHI3L1 levels correlated with each other (r = 0.58), and with IgM-oligoclonal bands (p = 0.02 and p = 0.004, respectively). In addition, CSF CHI3L1 concentration was a predictor for 1-point EDSS worsening {HR = 2.99 [95% CI (1.27, 7.07)]} and progression during follow-up {HR = 18 [95% CI (2.31, 141.3)]}. The pattern of combined measure of biomarkers was useful to discriminate MS phenotypes and to anticipate clinical progression: RRMS more frequently presented high NFL combined with low CHI3L1 levels, compared to SPMS (HR 0.41 [0.18–0.82]), and PPMS (HR 0.46 [0.19–0.87]), while elevation of both biomarkers preceded diagnosis of clinical progression in RRMS patients (log rank = 0.02).Conclusions: Individual measures of CSF NFL and CHI3L1 are biomarkers of disease activity and progression, respectively. The pattern of combined measure discriminates MS phenotypes. It also predicts the subset of RRMS patients that will progress clinically allowing early intervention.https://www.frontiersin.org/article/10.3389/fneur.2019.01008/fullYKL-40CHI3L1NFLprogressive multiple sclerosisgadolinium-enhancing lesions |
| spellingShingle | Sara Gil-Perotin Sara Gil-Perotin Jessica Castillo-Villalba Jessica Castillo-Villalba Laura Cubas-Nuñez Laura Cubas-Nuñez Raquel Gasque David Hervas Josep Gomez-Mateu Carmen Alcala Francisco Perez-Miralles Francisco Gascon Jose Andres Dominguez Bonaventura Casanova Bonaventura Casanova Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple Sclerosis Frontiers in Neurology YKL-40 CHI3L1 NFL progressive multiple sclerosis gadolinium-enhancing lesions |
| title | Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple Sclerosis |
| title_full | Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple Sclerosis |
| title_fullStr | Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple Sclerosis |
| title_full_unstemmed | Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple Sclerosis |
| title_short | Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple Sclerosis |
| title_sort | combined cerebrospinal fluid neurofilament light chain protein and chitinase 3 like 1 levels in defining disease course and prognosis in multiple sclerosis |
| topic | YKL-40 CHI3L1 NFL progressive multiple sclerosis gadolinium-enhancing lesions |
| url | https://www.frontiersin.org/article/10.3389/fneur.2019.01008/full |
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