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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Detalles Bibliográficos
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
Descripción
Sumario: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.

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