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Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS.
Fernández-Velasco, José I; Kuhle, Jens; Monreal, Enric; Meca-Lallana, Virginia; Meca-Lallana, José; Izquierdo, Guillermo; Gascón-Giménez, Francisco; Sainz de la Maza, Susana; Walo-Delgado, Paulette E; Maceski, Aleksandra; Rodríguez-Martín, Eulalia; Roldán, Ernesto; Villarrubia, Noelia; Saiz, Albert; Blanco, Yolanda; Sánchez, Pedro; Carreón-Guarnizo, Ester; Aladro, Yolanda; Brieva, Luis; Íñiguez, Cristina; González-Suárez, Inés; Rodríguez de Antonio, Luis A; Masjuan, Jaime; Costa-Frossard, Lucienne; Villar, Luisa M.
Afiliación
  • Fernández-Velasco JI; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Kuhle J; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Monreal E; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Meca-Lallana V; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Meca-Lallana J; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Izquierdo G; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Gascón-Giménez F; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Sainz de la Maza S; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Walo-Delgado PE; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Maceski A; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Rodríguez-Martín E; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Roldán E; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Villarrubia N; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Saiz A; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Blanco Y; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Sánchez P; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Carreón-Guarnizo E; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Aladro Y; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Brieva L; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Íñiguez C; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • González-Suárez I; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Rodríguez de Antonio LA; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Masjuan J; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Costa-Frossard L; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
  • Villar LM; From the Immunology Department (J.I.F.-V., P.E.W.-D., E.R.-M., E.R., N.V., L.M.V.), Ramon y Cajal University Hospital, Madrid, Spain; Neurologic Clinic and Policlinic (J.K., A.M.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerlan
Neurol Neuroimmunol Neuroinflamm ; 8(2)2021 03 04.
Article en En | MEDLINE | ID: mdl-33408167
ABSTRACT

OBJECTIVE:

To analyze the changes induced by ocrelizumab in blood immune cells of patients with primary progressive MS (PPMS).

METHODS:

In this multicenter prospective study including 53 patients with PPMS who initiated ocrelizumab treatment, we determined effector, memory, and regulatory cells by flow cytometry at baseline and after 6 months of therapy. Wilcoxon matched paired tests were used to assess differences between baseline and 6 months' results. p Values were corrected using the Bonferroni test.

RESULTS:

Ocrelizumab reduced the numbers of naive and memory B cells (p < 0.0001) and those of B cells producing interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNFα) (p < 0.0001 in all cases). By contrast, the proportions of plasmablasts and B cells producing GM-CSF and TNFα increased significantly, suggesting the need for treatment continuation. We also observed a decrease in CD20+ T-cell numbers (p < 0.0001) and percentages (p < 0.0001), and a clear remodeling of the T-cell compartment characterized by relative increases of the naive/effector ratios in CD4+ (p = 0.002) and CD8+ (p = 0.002) T cells and relative decreases of CD4+ (p = 0.03) and CD8+ (p = 0.004) T cells producing interferon-gamma. Total monocyte numbers increased (p = 0.002), but no changes were observed in those producing inflammatory cytokines. The immunologic variations were associated with a reduction of serum neurofilament light chain (sNfL) levels (p = 0.008). The reduction was observed in patients with Gd-enhanced lesions at baseline and in Gd- patients with baseline sNfL >10 pg/mL.

CONCLUSIONS:

In PPMS, effector B-cell depletion changed T-cell response toward a low inflammatory profile, resulting in decreased sNfL levels.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Esclerosis Múltiple Crónica Progresiva / Anticuerpos Monoclonales Humanizados / Factores Inmunológicos / Leucocitos Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Neurol Neuroimmunol Neuroinflamm Año: 2021 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Esclerosis Múltiple Crónica Progresiva / Anticuerpos Monoclonales Humanizados / Factores Inmunológicos / Leucocitos Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Neurol Neuroimmunol Neuroinflamm Año: 2021 Tipo del documento: Article