Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS
| Autor: | Inés González-Suárez, Pedro Sánchez, Guillermo Izquierdo, C Iñiguez, Eulalia Rodríguez-Martín, Lucienne Costa-Frossard, Luisa M. Villar, Yolanda Blanco, Noelia Villarrubia, Jose Ignacio Fernández-Velasco, Luis Brieva, Yolanda Aladro, Ester Carreón-Guarnizo, Luis A. Rodríguez de Antonio, Jaime Masjuan, Enric Monreal, Aleksandra Maceski, José Meca-Lallana, Susana Sainz de la Maza, Francisco Gascón-Giménez, Albert Saiz, Jens Kuhle, Ernesto Roldán, Paulette Esperanza Walo-Delgado, Virginia Meca-Lallana |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Wilcoxon signed-rank test Antibodies Monoclonal Humanized Article Flow cytometry Primary progressive 03 medical and health sciences symbols.namesake 0302 clinical medicine Text mining Immune system Internal medicine Leukocytes medicine Humans Immunologic Factors Longitudinal Studies Prospective Studies Prospective cohort study Aged medicine.diagnostic_test business.industry Middle Aged Multiple Sclerosis Chronic Progressive Treatment Outcome 030104 developmental biology Bonferroni correction Neurology symbols Female Ocrelizumab Neurology (clinical) business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neurology® Neuroimmunology & Neuroinflammation article-version (Version of Record) 3 |
| ISSN: | 2332-7812 |
| DOI: | 10.1212/nxi.0000000000000940 |
| Popis: | ObjectiveTo analyze the changes induced by ocrelizumab in blood immune cells of patients with primary progressive MS (PPMS).MethodsIn 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.ResultsOcrelizumab 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.ConclusionsIn PPMS, effector B-cell depletion changed T-cell response toward a low inflammatory profile, resulting in decreased sNfL levels. |
| Databáze: | OpenAIRE |
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