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.
Glossary
- EM=
- effector memory;
- GM-CSF=
- granulocyte-macrophage colony-stimulating factor;
- IFN-γ=
- interferon-gamma;
- Ig=
- immunoglobulin;
- IL=
- interleukin;
- NK=
- natural killer;
- PBMC=
- peripheral blood mononuclear cell;
- PD-L1=
- programmed death-ligand 1;
- PPMS=
- primary progressive MS;
- RRMS=
- relapsing-remitting MS;
- sNfL=
- serum neurofilament light chain;
- TD=
- terminally differentiated;
- TNFα=
- tumor necrosis factor-alpha
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by PI18/00572 integrated in the Plan Estatal I+D+I and cofunded by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER, “Otra manera de hacer Europa”).
- Received July 14, 2020.
- Accepted in final form November 3, 2020.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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