Alterations in the innate and adaptive immune system in a real-world cohort of multiple sclerosis patients treated with ocrelizumab

L Beckers; P Baeten; V Popescu; D Swinnen; A Cardilli; I Hamad; B Van Wijmeersch; S J Tavernier; M Kleinewietfeld; B Broux; J Fraussen; V Somers

doi:10.1016/j.clim.2024.109894

Alterations in the innate and adaptive immune system in a real-world cohort of multiple sclerosis patients treated with ocrelizumab

Clin Immunol. 2024 Feb:259:109894. doi: 10.1016/j.clim.2024.109894. Epub 2024 Jan 6.

Authors

L Beckers¹, P Baeten¹, V Popescu², D Swinnen³, A Cardilli³, I Hamad³, B Van Wijmeersch², S J Tavernier⁴, M Kleinewietfeld³, B Broux¹, J Fraussen¹, V Somers⁵

Affiliations

¹ University MS Center (UMSC), Hasselt-Pelt, Hasselt, Belgium; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
² University MS Center (UMSC), Hasselt-Pelt, Hasselt, Belgium; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Hasselt, Belgium; Noorderhart, Rehabilitation and MS Center, Pelt, Belgium.
³ University MS Center (UMSC), Hasselt-Pelt, Hasselt, Belgium; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Hasselt, Belgium; VIB Laboratory of Translational Immunomodulation, Center for Inflammation Research (IRC), Diepenbeek, Belgium.
⁴ Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research (IRC), Ghent, Belgium.
⁵ University MS Center (UMSC), Hasselt-Pelt, Hasselt, Belgium; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Hasselt, Belgium. Electronic address: veerle.somers@uhasselt.be.

PMID: 38185268
DOI: 10.1016/j.clim.2024.109894

Abstract

B cell depletion by the anti-CD20 antibody ocrelizumab is effective in relapsing-remitting (RR) and primary progressive (PP) multiple sclerosis (MS). We investigated immunological changes in peripheral blood of a real-world MS cohort after 6 and 12 months of ocrelizumab. All RRMS and most PPMS patients (15/20) showed treatment response. Ocrelizumab not only reduced CD20⁺ B cells, but also numbers of CD20⁺ T cells. Absolute numbers of monocytes, dendritic cells and CD8⁺ T cells were increased, while CD56^hi natural killer cells were reduced after ocrelizumab. The residual B cell population shifted towards transitional and activated, IgA⁺ switched memory B cells, double negative B cells, and antibody-secreting cells. Delaying the treatment interval by 2-3 months increased mean B cell frequencies and enhanced naive B cell repopulation. Ocrelizumab reduced plasma levels of interleukin(IL)-12p70 and interferon(IFN)-α2. These findings will contribute to understanding ineffective treatment responses, dealing with life-threatening infections and further unravelling MS pathogenesis.

Keywords: B cells; Extended interval dosing; High-dimensional flow cytometry; Multiple sclerosis; Ocrelizumab; Treatment response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized*
CD8-Positive T-Lymphocytes
Humans
Immune System
Immunologic Factors / therapeutic use
Interleukin-12
Multiple Sclerosis* / drug therapy
Multiple Sclerosis, Relapsing-Remitting* / drug therapy

Substances

ocrelizumab
Immunologic Factors
Interleukin-12
Antibodies, Monoclonal, Humanized