Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2021 Jan 6;8(2):e940.
doi: 10.1212/NXI.0000000000000940. Print 2021 Mar 4.

Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS

José I Fernández-Velasco  1 , Jens Kuhle  1 , Enric Monreal  1 , Virginia Meca-Lallana  1 , José Meca-Lallana  1 , Guillermo Izquierdo  1 , Francisco Gascón-Giménez  1 , Susana Sainz de la Maza  1 , Paulette E Walo-Delgado  1 , Aleksandra Maceski  1 , Eulalia Rodríguez-Martín  1 , Ernesto Roldán  1 , Noelia Villarrubia  1 , Albert Saiz  1 , Yolanda Blanco  1 , Pedro Sánchez  1 , Ester Carreón-Guarnizo  1 , Yolanda Aladro  1 , Luis Brieva  1 , Cristina Íñiguez  1 , Inés González-Suárez  1 , Luis A Rodríguez de Antonio  1 , Jaime Masjuan  1 , Lucienne Costa-Frossard  1 , Luisa M Villar  2
Affiliations
Multicenter Study

Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS

José I Fernández-Velasco et al. Neurol Neuroimmunol Neuroinflamm. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Changes in Blood B-Cell Subsets on Ocrelizumab Treatment
B-cell subsets were obtained before (0M) and at 6 months (6M) of ocrelizumab treatment (n = 53). (A) Absolute numbers (cells/μL) of the different CD19+ B-cell subsets. (B) Percentages of the CD19+ B-cell subsets related to total CD19+ cells. (C) Absolute numbers (cells/μL) of CD19+ cytokine-producing cells. (D) Percentages of CD19+ cytokine-producing cells related to total CD19+ cells. Median and 25%–75% interquartile range values are shown. **p < 0.01, ****p < 0.0001. GM-CSF = granulocyte-macrophage colony-stimulating factor; IL = interleukin; MemB = memory B cell; PB = plasmablasts; TNF = tumor necrosis factor; TransB = transitional B cell.
Figure 2
Figure 2. Changes in Blood T Cells Induced by Ocrelizumab Treatment
Percentages of CD4+ (A) and CD8+ (B) T-cell subsets, referred to total CD4+ and CD8+ T cells, respectively, obtained before (0M) and at 6 months (6M) of ocrelizumab treatment (n = 53). Median and 25%–75% interquartile range values are shown. *p < 0.05, ***p < 0.001, ****p < 0.0001.CM = central memory; EM = effector memory; TD = terminally differentiated.
Figure 3
Figure 3. Ocrelizumab Treatment Induces Changes in sNfL Levels
sNfL levels (pg/mL) obtained before (0M) and at 6 months (6M) of ocrelizumab treatment (n = 53). (A) All patients. (B) Patients showing gadolinium-enhanced lesions (Gd+) at baseline. (C) Patients not showing gadolinium-enhanced lesions (Gd−) with sNfL levels >10 pg/mL at baseline. (D) Patients not showing gadolinium-enhanced lesions (Gd−) with sNfL levels ≤10 pg/mL at baseline. sNfL = serum neurofilament light chain.
See this image and copyright information in PMC

References

    1. Faissner S, Plemel J, Gold R, Yong W. Progressive multiple sclerosis: from pathophysiology to therapeutic strategies. Nat Rev Drug Discov 2019;18:905–922. - PubMed
    1. Macaron G, Ontaneda D. Diagnosis and management of progressive multiple sclerosis. Biomedicines 2019;7:56. - PMC - PubMed
    1. Bittner S, Ruck T, Wiendl H, et al. . Targeting B cells in relapsing–remitting multiple sclerosis: from pathophysiology to optimal clinical management. Ther Adv Neurol Disord 2017;10:51–66. - PMC - PubMed
    1. Montalban X, Hauser SL, Kappos L, et al. . Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Eng J Med 2017;376:209–220. - PubMed
    1. Sorensen PS, Blinkenberg M. The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects. Ther Adv Neurol Disord 2016;9:44–52. - PMC - PubMed

Publication types