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

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

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Detalles Bibliográficos
Autores: Fernández-Velasco JI, Monreal E, Kuhle J, Meca-Lallana V, Meca-Lallana J, Izquierdo G, Oreja-Guevara C, Gascón-Giménez F, Sainz de la Maza S, Walo-Delgado PE, Lapuente-Suanzes P, Maceski A, Rodríguez-Martín E, Roldán E, Villarrubia N, Saiz A, Blanco Y, Diaz-Pérez C, Valero-López G, Diaz-Diaz J, Aladro Y, Brieva L, Íñiguez C, González-Suárez I, Rodríguez de Antonio LA, García-Domínguez JM, Sabin J, Llufriu S, Masjuan J, Costa-Frossard L, Villar LM
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p16790
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/16790
Access Level:acceso abierto
Palabra clave:B cells
biomarkers
demyelinating diseases
multiple sclerosis
ocrelizumab
Descripción
Sumario:OBJECTIVE: To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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