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Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis

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  1. Increased Intrathecal Activity of Follicular Helper T Cells in Patients With Relapsing-Remitting Multiple Sclerosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Leveraging Visual Outcome Measures to Advance Therapy Development in Neuroimmunologic Disorders

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  1. Extended dosing of monoclonal antibodies in multiple sclerosis

    Research output: Contribution to journalReviewResearchpeer-review

  2. Linking lesions in sensorimotor cortex to contralateral hand function in multiple sclerosis: a 7 T MRI study

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  3. All anti-CD20 monoclonal antibodies have similar efficacy and risks: No

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Increased Intrathecal Activity of Follicular Helper T Cells in Patients With Relapsing-Remitting Multiple Sclerosis

    Research output: Contribution to journalJournal articleResearchpeer-review

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BACKGROUND AND OBJECTIVES: The anti-CD20 antibody ofatumumab is an efficacious therapy for multiple sclerosis (MS) through depletion of B cells. The purpose of this study was to examine the derivative effects of B cell depletion on the peripheral immune system and a direct treatment effect on T cells expressing CD20.

METHODS: Frequency and absolute numbers of peripheral leukocytes of treatment-naive patients with relapsing-remitting MS (RRMS) and patients treated with ofatumumab for a mean of 482 days were assessed in this observational study by flow cytometry. In addition, effector function and CNS migration of T cells using a human in vitro blood-brain barrier (BBB) assay were analyzed.

RESULTS: This study showed that ofatumumab treatment of patients with RRMS increased the control of effector T cells and decreased T cell autoreactivity. It also showed that ofatumumab reduced the level of peripheral CD20+ T cells and that the observed decrease in CNS-migratory capacity of T cells was caused by the depletion of CD20+ T cells. Finally, our study pointed out a bias in the measurement of CD20+ cells due to a steric hindrance between the treatment antibody and the flow cytometry antibody.

DISCUSSION: The substantial ofatumumab-induced alteration in the T cell compartment including a severely decreased CNS-migratory capacity of T cells could partly be attributed to the depletion of CD20+ T cells. Therefore, we propose that depletion of CD20+ T cells contributes to the positive treatment effect of ofatumumab and suggests that ofatumumab therapy should be considered a B cell and CD20+ T cell depletion therapy.

CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that compared with treatment-naive patients, ofatumumab treatment of patients with RRMS decreases peripheral CD20+ T cells, increases effector T cell control, and decreases T cell autoreactivity.

Original languageEnglish
Article numbere200004
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume9
Issue number4
ISSN2332-7812
DOIs
Publication statusPublished - Jul 2022

Bibliographical note

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

    Research areas

  • Antibodies, Monoclonal, Humanized/adverse effects, Antigens, CD20, Humans, Multiple Sclerosis/drug therapy, T-Lymphocytes

ID: 78438974