Neurology®, Neuroimmunology, and Neuroinflammation | January 6, 2021

Fernández-Velasco JI, Kuhle J, Monreal E, Meca-Lallana V, Meca-Lallana J, Izquierdo G, Gascón-Giménez F, Sainz de la Maza S, Walo-Delgado PE, Maceski A, Rodríguez-Martín E, Roldán E, Villarrubia N, Saiz A, Blanco Y, Sánchez P, Carreón-Guarnizo E, Aladro Y, Brieva L, Íñiguez C, González-Suárez I, Rodríguez de Antonio LA, Masjuan J, Costa-Frossard L and Villar LM

Neurol Neuroimmunol Neuroinflamm. 2021 Jan 6;8(2):e940

DOI: 10.1212/NXI.0000000000000940

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.