Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment

Abstract Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing–remitting MS patients initi...

Full description

Bibliographic Details
Main Authors: Paulette Esperanza Walo-Delgado, Susana Sainz de la Maza, Noelia Villarrubia, Enric Monreal, Silvia Medina, Mercedes Espiño, José Ignacio Fernández-Velasco, Eulalia Rodríguez-Martín, Ernesto Roldán, Daniel Lourido, Alfonso Muriel, Jaime Masjuan-Vallejo, Lucienne Costa-Frossard, Luisa María Villar
Format: Article
Language:English
Published: Nature Publishing Group 2021-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-88624-7
id doaj-8c728d8ae2de49b8accdc64e3ffacaf7
record_format Article
spelling doaj-8c728d8ae2de49b8accdc64e3ffacaf72021-05-02T11:32:46ZengNature Publishing GroupScientific Reports2045-23222021-04-011111810.1038/s41598-021-88624-7Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatmentPaulette Esperanza Walo-Delgado0Susana Sainz de la Maza1Noelia Villarrubia2Enric Monreal3Silvia Medina4Mercedes Espiño5José Ignacio Fernández-Velasco6Eulalia Rodríguez-Martín7Ernesto Roldán8Daniel Lourido9Alfonso Muriel10Jaime Masjuan-Vallejo11Lucienne Costa-Frossard12Luisa María Villar13Immunology Department, Ramón y Cajal University Hospital, IRYCIS, REEMNeurology Department, Ramón y Cajal University Hospital, IRYCIS, REEMImmunology Department, Ramón y Cajal University Hospital, IRYCIS, REEMNeurology Department, Ramón y Cajal University Hospital, IRYCIS, REEMImmunology Department, Ramón y Cajal University Hospital, IRYCIS, REEMImmunology Department, Ramón y Cajal University Hospital, IRYCIS, REEMImmunology Department, Ramón y Cajal University Hospital, IRYCIS, REEMImmunology Department, Ramón y Cajal University Hospital, IRYCIS, REEMImmunology Department, Ramón y Cajal University Hospital, IRYCIS, REEMRadiology Department, Ramón y Cajal University Hospital, IRYCIS, REEMClinical Biostatistics Unit, Ramón y Cajal University Hospital, IRYCIS, University of Alcalá, CIBERESPNeurology Department, Ramón y Cajal University Hospital, IRYCIS, REEMNeurology Department, Ramón y Cajal University Hospital, IRYCIS, REEMImmunology Department, Ramón y Cajal University Hospital, IRYCIS, REEMAbstract Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing–remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Blood lymphocyte subsets were measured at baseline and at 6 months by flow cytometry. Patients were followed a year and classified as NEDA (no evidence of disease activity) or ODA (ongoing disease activity). NEDA patients had lower sNfL levels at baseline (p = 0.0001), and after three (p = 0.004) and six (p = 0.03) months of DMF treatment. Consequently, low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82–15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p < 0.0001). This shows that low baseline sNfL values identify MS patients with higher probability of optimal response to DMF and of a reduction in effector immune cells.https://doi.org/10.1038/s41598-021-88624-7
collection DOAJ
language English
format Article
sources DOAJ
author Paulette Esperanza Walo-Delgado
Susana Sainz de la Maza
Noelia Villarrubia
Enric Monreal
Silvia Medina
Mercedes Espiño
José Ignacio Fernández-Velasco
Eulalia Rodríguez-Martín
Ernesto Roldán
Daniel Lourido
Alfonso Muriel
Jaime Masjuan-Vallejo
Lucienne Costa-Frossard
Luisa María Villar
spellingShingle Paulette Esperanza Walo-Delgado
Susana Sainz de la Maza
Noelia Villarrubia
Enric Monreal
Silvia Medina
Mercedes Espiño
José Ignacio Fernández-Velasco
Eulalia Rodríguez-Martín
Ernesto Roldán
Daniel Lourido
Alfonso Muriel
Jaime Masjuan-Vallejo
Lucienne Costa-Frossard
Luisa María Villar
Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment
Scientific Reports
author_facet Paulette Esperanza Walo-Delgado
Susana Sainz de la Maza
Noelia Villarrubia
Enric Monreal
Silvia Medina
Mercedes Espiño
José Ignacio Fernández-Velasco
Eulalia Rodríguez-Martín
Ernesto Roldán
Daniel Lourido
Alfonso Muriel
Jaime Masjuan-Vallejo
Lucienne Costa-Frossard
Luisa María Villar
author_sort Paulette Esperanza Walo-Delgado
title Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment
title_short Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment
title_full Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment
title_fullStr Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment
title_full_unstemmed Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment
title_sort low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-04-01
description Abstract Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing–remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Blood lymphocyte subsets were measured at baseline and at 6 months by flow cytometry. Patients were followed a year and classified as NEDA (no evidence of disease activity) or ODA (ongoing disease activity). NEDA patients had lower sNfL levels at baseline (p = 0.0001), and after three (p = 0.004) and six (p = 0.03) months of DMF treatment. Consequently, low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82–15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p < 0.0001). This shows that low baseline sNfL values identify MS patients with higher probability of optimal response to DMF and of a reduction in effector immune cells.
url https://doi.org/10.1038/s41598-021-88624-7
work_keys_str_mv AT pauletteesperanzawalodelgado lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT susanasainzdelamaza lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT noeliavillarrubia lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT enricmonreal lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT silviamedina lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT mercedesespino lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT joseignaciofernandezvelasco lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT eulaliarodriguezmartin lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT ernestoroldan lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT daniellourido lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT alfonsomuriel lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT jaimemasjuanvallejo lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT luciennecostafrossard lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
AT luisamariavillar lowserumneurofilamentlightchainvaluesidentifyoptimalresponderstodimethylfumarateinmultiplesclerosistreatment
_version_ 1721492081020502016