Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple Sclerosis.

Fecha de publicación: 23/09/2019

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

Castillo-Villalba J
Cubas-Nuñez L
Gasque R
Gomez-Mateu J
Alcala C
Gascon F
Dominguez JA

Grupos

Investigación en Neuroinmunología y Esclerosis Múltiple

Leader

Bonaventura Casanova Estruch

Abstract

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.

Datos de la publicación

ISSN/ISSNe:: 1664-2295, 1664-2295
Tipo:: Article
Páginas:: 1008-1008
DOI:: 10.3389/fneur.2019.01008
Factor de Impacto:: 1,062 SCImago ℠
Cuartil:: Q2 SCImago ℠

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Métricas

Filiaciones

Gil-Perotin S:: Multiple Sclerosis Unit, Hospital Universitari I Politècnic La Fe, Valencia, Spain

Instituto de Investigación. Research Group in Neuroimmunology, Health Research Institute La Fe, Valencia, Spain
Castillo-Villalba J:: Multiple Sclerosis Unit, Hospital Universitari I Politècnic La Fe, Valencia, Spain

Instituto de Investigación. Research Group in Neuroimmunology, Health Research Institute La Fe, Valencia, Spain
Cubas-Nuñez L:: Multiple Sclerosis Unit, Hospital Universitari I Politècnic La Fe, Valencia, Spain

Instituto de Investigación. Research Group in Neuroimmunology, Health Research Institute La Fe, Valencia, Spain
Gasque R:: Instituto de Investigación. Research Group in Neuroimmunology, Health Research Institute La Fe, Valencia, Spain
Hervas D:: Instituto de Investigación. Biostatistics Unit, Health Research Institute La Fe, Valencia, Spain
Gomez-Mateu J:: Neurology Department, Hospital Universitari Dr. Peset, Valencia, Spain
Alcala C:: Multiple Sclerosis Unit, Hospital Universitari I Politècnic La Fe, Valencia, Spain
Perez-Miralles F:: Multiple Sclerosis Unit, Hospital Universitari I Politècnic La Fe, Valencia, Spain
Gascon F:: Neuroimmunology Unit, Hospital Clínic de València, Valencia, Spain
Dominguez JA:: Neuroimmunology Unit, Hospital Clínic de València, Valencia, Spain
Casanova B:: Multiple Sclerosis Unit, Hospital Universitari I Politècnic La Fe, Valencia, Spain

Instituto de Investigación. Research Group in Neuroimmunology, Health Research Institute La Fe, Valencia, Spain

Keywords

CHI3L1, NFL, YKL-40, gadolinium-enhancing lesions, progressive multiple sclerosis

Campos de estudio

Proyectos asociados

PROYECTO CAIBER

CAI08/01/0061 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009

RED DE BIOBANCOS (BIOBANCOS)

RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

PATRONES DE RM CEREBRAL Y MEDULAR EN RELACION CON LA PRESENCIA DE AUTOANTIGENOS NEURONALES RECONOCIDOS POR INMUNOGLOBULINAS M PRESENTES EN EL LIQUIDO CEFALORRAQUIDEO DE PACIENTES DE ESCLEROSIS MULTIPLE.

Investigador Principal: ISABEL BOSCÁ BLASCO

MERCK SERONO DR. CASANOVA . ALMIRALL S.A; FUNDACIÓN BIOGEN IDEC; MERCK S.L.U; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010