Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology

To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS).Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gad...

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Autores: Fernández Velasco, José I., Monreal, Enric, Kuhle, Jens, Meca Lallana, Virginia, Meca Lallana, José E., Izquierdo, Guillermo, Oreja-Guevara, Celia, Gascón Gimenez, Francisco, Sainz de la Maza, Susana, Walo Delgado, Paulette E., Lapuente Suanzes, Paloma, Maceski, Aleksandra, Rodriguez Martín, Eulalia, Roldán, Ernesto, Villarrubia, Noelia, Saiz Hinarejos, Albert, Blanco, Yolanda, Diaz Pérez, Carolina, Valero López, Gabriel, Díaz Díaz, Judit, Aladro, Yolanda, Brieva, Luis, Iñíguez, Cristina, González Suárez, Inés, Rodríguez de Antonio, Luis A., García Domínguez, José M., Sabin, Julia, Llufriu Duran, Sara, Masjuan, Jaime, Costa Frossard, Lucienne, Villar, Luisa M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/201067
Acceso en línea:https://hdl.handle.net/2445/201067
Access Level:acceso abierto
Palabra clave:Esclerosi múltiple
Imatges per ressonància magnètica
Multiple sclerosis
Magnetic resonance imaging
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repository_id_str
spelling Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis PathologyFernández Velasco, José I.Monreal, EnricKuhle, JensMeca Lallana, VirginiaMeca Lallana, José E.Izquierdo, GuillermoOreja-Guevara, CeliaGascón Gimenez, FranciscoSainz de la Maza, SusanaWalo Delgado, Paulette E.Lapuente Suanzes, PalomaMaceski, AleksandraRodriguez Martín, EulaliaRoldán, ErnestoVillarrubia, NoeliaSaiz Hinarejos, AlbertBlanco, YolandaDiaz Pérez, CarolinaValero López, GabrielDíaz Díaz, JuditAladro, YolandaBrieva, LuisIñíguez, CristinaGonzález Suárez, InésRodríguez de Antonio, Luis A.García Domínguez, José M.Sabin, JuliaLlufriu Duran, SaraMasjuan, JaimeCosta Frossard, LucienneVillar, Luisa M.Esclerosi múltipleImatges per ressonància magnèticaMultiple sclerosisMagnetic resonance imagingTo ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS).Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula.More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels.Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms.Copyright © 2022 Fernández-Velasco, Monreal, Kuhle, Meca-Lallana, Meca-Lallana, Izquierdo, Oreja-Guevara, Gascón-Giménez, Sainz de la Maza, Walo-Delgado, Lapuente-Suanzes, Maceski, Rodríguez-Martín, Roldán, Villarrubia, Saiz, Blanco, Diaz-Pérez, Valero-López, Diaz-Diaz, Aladro, Brieva, Íñiguez, González-Suárez, Rodríguez de Antonio, García-Domínguez, Sabin, Llufriu, Masjuan, Costa-Frossard and Villar.2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/201067Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.842354Frontiers In Immunology, 2022, vol. 13https://doi.org/10.3389/fimmu.2022.842354cc by (c) Fernández Velasco, José I. et al, 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2010672026-05-27T06:46:51Z
dc.title.none.fl_str_mv Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology
title Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology
spellingShingle Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology
Fernández Velasco, José I.
Esclerosi múltiple
Imatges per ressonància magnètica
Multiple sclerosis
Magnetic resonance imaging
title_short Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology
title_full Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology
title_fullStr Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology
title_full_unstemmed Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology
title_sort Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology
dc.creator.none.fl_str_mv Fernández Velasco, José I.
Monreal, Enric
Kuhle, Jens
Meca Lallana, Virginia
Meca Lallana, José E.
Izquierdo, Guillermo
Oreja-Guevara, Celia
Gascón Gimenez, Francisco
Sainz de la Maza, Susana
Walo Delgado, Paulette E.
Lapuente Suanzes, Paloma
Maceski, Aleksandra
Rodriguez Martín, Eulalia
Roldán, Ernesto
Villarrubia, Noelia
Saiz Hinarejos, Albert
Blanco, Yolanda
Diaz Pérez, Carolina
Valero López, Gabriel
Díaz Díaz, Judit
Aladro, Yolanda
Brieva, Luis
Iñíguez, Cristina
González Suárez, Inés
Rodríguez de Antonio, Luis A.
García Domínguez, José M.
Sabin, Julia
Llufriu Duran, Sara
Masjuan, Jaime
Costa Frossard, Lucienne
Villar, Luisa M.
author Fernández Velasco, José I.
author_facet Fernández Velasco, José I.
Monreal, Enric
Kuhle, Jens
Meca Lallana, Virginia
Meca Lallana, José E.
Izquierdo, Guillermo
Oreja-Guevara, Celia
Gascón Gimenez, Francisco
Sainz de la Maza, Susana
Walo Delgado, Paulette E.
Lapuente Suanzes, Paloma
Maceski, Aleksandra
Rodriguez Martín, Eulalia
Roldán, Ernesto
Villarrubia, Noelia
Saiz Hinarejos, Albert
Blanco, Yolanda
Diaz Pérez, Carolina
Valero López, Gabriel
Díaz Díaz, Judit
Aladro, Yolanda
Brieva, Luis
Iñíguez, Cristina
González Suárez, Inés
Rodríguez de Antonio, Luis A.
García Domínguez, José M.
Sabin, Julia
Llufriu Duran, Sara
Masjuan, Jaime
Costa Frossard, Lucienne
Villar, Luisa M.
author_role author
author2 Monreal, Enric
Kuhle, Jens
Meca Lallana, Virginia
Meca Lallana, José E.
Izquierdo, Guillermo
Oreja-Guevara, Celia
Gascón Gimenez, Francisco
Sainz de la Maza, Susana
Walo Delgado, Paulette E.
Lapuente Suanzes, Paloma
Maceski, Aleksandra
Rodriguez Martín, Eulalia
Roldán, Ernesto
Villarrubia, Noelia
Saiz Hinarejos, Albert
Blanco, Yolanda
Diaz Pérez, Carolina
Valero López, Gabriel
Díaz Díaz, Judit
Aladro, Yolanda
Brieva, Luis
Iñíguez, Cristina
González Suárez, Inés
Rodríguez de Antonio, Luis A.
García Domínguez, José M.
Sabin, Julia
Llufriu Duran, Sara
Masjuan, Jaime
Costa Frossard, Lucienne
Villar, Luisa M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Esclerosi múltiple
Imatges per ressonància magnètica
Multiple sclerosis
Magnetic resonance imaging
topic Esclerosi múltiple
Imatges per ressonància magnètica
Multiple sclerosis
Magnetic resonance imaging
description To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS).Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula.More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels.Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms.Copyright © 2022 Fernández-Velasco, Monreal, Kuhle, Meca-Lallana, Meca-Lallana, Izquierdo, Oreja-Guevara, Gascón-Giménez, Sainz de la Maza, Walo-Delgado, Lapuente-Suanzes, Maceski, Rodríguez-Martín, Roldán, Villarrubia, Saiz, Blanco, Diaz-Pérez, Valero-López, Diaz-Diaz, Aladro, Brieva, Íñiguez, González-Suárez, Rodríguez de Antonio, García-Domínguez, Sabin, Llufriu, Masjuan, Costa-Frossard and Villar.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/201067
url https://hdl.handle.net/2445/201067
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.842354
Frontiers In Immunology, 2022, vol. 13
https://doi.org/10.3389/fimmu.2022.842354
dc.rights.none.fl_str_mv cc by (c) Fernández Velasco, José I. et al, 2022
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Fernández Velasco, José I. et al, 2022
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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