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Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis
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 cell...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Lippincott Williams & Wilkins
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272791/ https://www.ncbi.nlm.nih.gov/pubmed/35672145 http://dx.doi.org/10.1212/NXI.0000000000200004 |
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author | von Essen, Marina Rode Hansen, Rikke Holm Højgaard, Camilla Ammitzbøll, Cecilie Wiendl, Heinz Sellebjerg, Finn |
author_facet | von Essen, Marina Rode Hansen, Rikke Holm Højgaard, Camilla Ammitzbøll, Cecilie Wiendl, Heinz Sellebjerg, Finn |
author_sort | von Essen, Marina Rode |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9272791 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-92727912022-07-12 Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis von Essen, Marina Rode Hansen, Rikke Holm Højgaard, Camilla Ammitzbøll, Cecilie Wiendl, Heinz Sellebjerg, Finn Neurol Neuroimmunol Neuroinflamm Research Article 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. Lippincott Williams & Wilkins 2022-06-07 /pmc/articles/PMC9272791/ /pubmed/35672145 http://dx.doi.org/10.1212/NXI.0000000000200004 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Research Article von Essen, Marina Rode Hansen, Rikke Holm Højgaard, Camilla Ammitzbøll, Cecilie Wiendl, Heinz Sellebjerg, Finn Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis |
title | Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis |
title_full | Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis |
title_fullStr | Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis |
title_full_unstemmed | Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis |
title_short | Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis |
title_sort | ofatumumab modulates inflammatory t cell responses and migratory potential in patients with multiple sclerosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272791/ https://www.ncbi.nlm.nih.gov/pubmed/35672145 http://dx.doi.org/10.1212/NXI.0000000000200004 |
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