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Ocrelizumab Depletes CD20(+) T Cells in Multiple Sclerosis Patients

Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS). CD20 is mainly expressed b...

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Autores principales: Gingele, Stefan, Jacobus, Thais Langer, Konen, Franz Felix, Hümmert, Martin W., Sühs, Kurt-Wolfram, Schwenkenbecher, Philipp, Ahlbrecht, Jonas, Möhn, Nora, Müschen, Lars H., Bönig, Lena, Alvermann, Sascha, Schmidt, Reinhold E., Stangel, Martin, Jacobs, Roland, Skripuletz, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356421/
https://www.ncbi.nlm.nih.gov/pubmed/30597851
http://dx.doi.org/10.3390/cells8010012
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author Gingele, Stefan
Jacobus, Thais Langer
Konen, Franz Felix
Hümmert, Martin W.
Sühs, Kurt-Wolfram
Schwenkenbecher, Philipp
Ahlbrecht, Jonas
Möhn, Nora
Müschen, Lars H.
Bönig, Lena
Alvermann, Sascha
Schmidt, Reinhold E.
Stangel, Martin
Jacobs, Roland
Skripuletz, Thomas
author_facet Gingele, Stefan
Jacobus, Thais Langer
Konen, Franz Felix
Hümmert, Martin W.
Sühs, Kurt-Wolfram
Schwenkenbecher, Philipp
Ahlbrecht, Jonas
Möhn, Nora
Müschen, Lars H.
Bönig, Lena
Alvermann, Sascha
Schmidt, Reinhold E.
Stangel, Martin
Jacobs, Roland
Skripuletz, Thomas
author_sort Gingele, Stefan
collection PubMed
description Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS). CD20 is mainly expressed by B cells, but a subset of T cells (CD3(+)CD20(+) T cells) also expresses CD20, and these CD20(+) T cells are known to be a highly activated cell population. The blood of MS patients was analyzed with multicolor flow cytometry before and two weeks after treatment with ocrelizumab regarding the phenotype of peripheral blood mononuclear cells. CD20-expressing CD3(+) T cells were found in blood samples of all MS patients, accounted for 2.4% of CD45(+) lymphocytes, and constituted a significant proportion (18.4%) of all CD20(+) cells. CD3(+)CD20(+) T cells and CD19(+)CD20(+) B cells were effectively depleted two weeks after a single administration of 300 mg ocrelizumab. Our results demonstrate that treatment with ocrelizumab does not exclusively target B cells, but also CD20(+) T cells, which account for a substantial amount of CD20-expressing cells. Thus, we speculate that the efficacy of ocrelizumab might also be mediated by the depletion of CD20-expressing T cells.
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spelling pubmed-63564212019-02-06 Ocrelizumab Depletes CD20(+) T Cells in Multiple Sclerosis Patients Gingele, Stefan Jacobus, Thais Langer Konen, Franz Felix Hümmert, Martin W. Sühs, Kurt-Wolfram Schwenkenbecher, Philipp Ahlbrecht, Jonas Möhn, Nora Müschen, Lars H. Bönig, Lena Alvermann, Sascha Schmidt, Reinhold E. Stangel, Martin Jacobs, Roland Skripuletz, Thomas Cells Brief Report Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS). CD20 is mainly expressed by B cells, but a subset of T cells (CD3(+)CD20(+) T cells) also expresses CD20, and these CD20(+) T cells are known to be a highly activated cell population. The blood of MS patients was analyzed with multicolor flow cytometry before and two weeks after treatment with ocrelizumab regarding the phenotype of peripheral blood mononuclear cells. CD20-expressing CD3(+) T cells were found in blood samples of all MS patients, accounted for 2.4% of CD45(+) lymphocytes, and constituted a significant proportion (18.4%) of all CD20(+) cells. CD3(+)CD20(+) T cells and CD19(+)CD20(+) B cells were effectively depleted two weeks after a single administration of 300 mg ocrelizumab. Our results demonstrate that treatment with ocrelizumab does not exclusively target B cells, but also CD20(+) T cells, which account for a substantial amount of CD20-expressing cells. Thus, we speculate that the efficacy of ocrelizumab might also be mediated by the depletion of CD20-expressing T cells. MDPI 2018-12-28 /pmc/articles/PMC6356421/ /pubmed/30597851 http://dx.doi.org/10.3390/cells8010012 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Gingele, Stefan
Jacobus, Thais Langer
Konen, Franz Felix
Hümmert, Martin W.
Sühs, Kurt-Wolfram
Schwenkenbecher, Philipp
Ahlbrecht, Jonas
Möhn, Nora
Müschen, Lars H.
Bönig, Lena
Alvermann, Sascha
Schmidt, Reinhold E.
Stangel, Martin
Jacobs, Roland
Skripuletz, Thomas
Ocrelizumab Depletes CD20(+) T Cells in Multiple Sclerosis Patients
title Ocrelizumab Depletes CD20(+) T Cells in Multiple Sclerosis Patients
title_full Ocrelizumab Depletes CD20(+) T Cells in Multiple Sclerosis Patients
title_fullStr Ocrelizumab Depletes CD20(+) T Cells in Multiple Sclerosis Patients
title_full_unstemmed Ocrelizumab Depletes CD20(+) T Cells in Multiple Sclerosis Patients
title_short Ocrelizumab Depletes CD20(+) T Cells in Multiple Sclerosis Patients
title_sort ocrelizumab depletes cd20(+) t cells in multiple sclerosis patients
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356421/
https://www.ncbi.nlm.nih.gov/pubmed/30597851
http://dx.doi.org/10.3390/cells8010012
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