José I Fernández-Velasco1, Jens Kuhle1, Enric Monreal1, Virginia Meca-Lallana1, José Meca-Lallana1, Guillermo Izquierdo1, Francisco Gascón-Giménez1, Susana Sainz de la Maza1, Paulette E Walo-Delgado1, Aleksandra Maceski1, Eulalia Rodríguez-Martín1, Ernesto Roldán1, Noelia Villarrubia1, Albert Saiz1, Yolanda Blanco1, Pedro Sánchez1, Ester Carreón-Guarnizo1, Yolanda Aladro1, Luis Brieva1, Cristina Íñiguez1, Inés González-Suárez1, Luis A Rodríguez de Antonio1, Jaime Masjuan1, Lucienne Costa-Frossard1, Luisa M Villar2. 1. 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, Switzerland; Neurology Department (E.M., S.S.d.l.M., J.M., L.C.-F.), Ramon y Cajal University Hospital, Madrid; Neurology Department (V.M.-L., P.S.), La Princesa University Hospital, Madrid; Multiple Sclerosis and Clinical Neuroimmunology Unit (J.M.-L., E.C.-G.), Virgen de la Arrixaca University Hospital, Murcia; Multiple Sclerosis Unit (G.I.), Vithas Nisa Sevilla Hospital; Neurology Department (F.G.-G.), Valencia Clinic University Hospital; Center of Neuroimmunology (A.S., Y.B.), Neurology Department, Clínic of Barcelona Hospital, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and Institut de Neurociències, Universitat de Barcelona; Neurology Department (Y.A.), Getafe University Hospital, Madrid; Neurology Department (L.B.), Arnau de Vilanova Hospital, Lleida; Neurology Department (C.Í.), Lozano Blesa Clinic University Hospital, Zaragoza; Neurology Department (I.G.-S.), Alvaro Cunqueiro Hospital, Vigo; Neurology Department (L.A.R.d.A.), Fuenlabrada University Hospital, Madrid, Spain. 2. 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, Switzerland; Neurology Department (E.M., S.S.d.l.M., J.M., L.C.-F.), Ramon y Cajal University Hospital, Madrid; Neurology Department (V.M.-L., P.S.), La Princesa University Hospital, Madrid; Multiple Sclerosis and Clinical Neuroimmunology Unit (J.M.-L., E.C.-G.), Virgen de la Arrixaca University Hospital, Murcia; Multiple Sclerosis Unit (G.I.), Vithas Nisa Sevilla Hospital; Neurology Department (F.G.-G.), Valencia Clinic University Hospital; Center of Neuroimmunology (A.S., Y.B.), Neurology Department, Clínic of Barcelona Hospital, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and Institut de Neurociències, Universitat de Barcelona; Neurology Department (Y.A.), Getafe University Hospital, Madrid; Neurology Department (L.B.), Arnau de Vilanova Hospital, Lleida; Neurology Department (C.Í.), Lozano Blesa Clinic University Hospital, Zaragoza; Neurology Department (I.G.-S.), Alvaro Cunqueiro Hospital, Vigo; Neurology Department (L.A.R.d.A.), Fuenlabrada University Hospital, Madrid, Spain. villarluisa88@gmail.com.
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.
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.
Authors: Carla Rodriguez-Mogeda; Sabela Rodríguez-Lorenzo; Jiji Attia; Jack van Horssen; Maarten E Witte; Helga E de Vries Journal: Biomolecules Date: 2022-06-07
Authors: José I Fernández-Velasco; Enric Monreal; Jens Kuhle; Virginia Meca-Lallana; José Meca-Lallana; Guillermo Izquierdo; Celia Oreja-Guevara; Francisco Gascón-Giménez; Susana Sainz de la Maza; Paulette E Walo-Delgado; Paloma Lapuente-Suanzes; Aleksandra Maceski; Eulalia Rodríguez-Martín; Ernesto Roldán; Noelia Villarrubia; Albert Saiz; Yolanda Blanco; Carolina Diaz-Pérez; Gabriel Valero-López; Judit Diaz-Diaz; Yolanda Aladro; Luis Brieva; Cristina Íñiguez; Inés González-Suárez; Luis A Rodríguez de Antonio; José M García-Domínguez; Julia Sabin; Sara Llufriu; Jaime Masjuan; Lucienne Costa-Frossard; Luisa M Villar Journal: Front Immunol Date: 2022-03-21 Impact factor: 7.561
Authors: Yakov A Lomakin; Ivan V Zvyagin; Leyla A Ovchinnikova; Marsel R Kabilov; Dmitriy B Staroverov; Artem Mikelov; Alexey E Tupikin; Maria Y Zakharova; Nadezda A Bykova; Vera S Mukhina; Alexander V Favorov; Maria Ivanova; Taras Simaniv; Yury P Rubtsov; Dmitriy M Chudakov; Maria N Zakharova; Sergey N Illarioshkin; Alexey A Belogurov; Alexander G Gabibov Journal: Front Immunol Date: 2022-08-16 Impact factor: 8.786