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Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS
José I Fernández-Velasco1, Jens Kuhle1, Enric Monreal1
1From 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.
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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