Rapid depletion of CD20 + B and T cells following ofatumumab therapy onset.

Autor: Konen FF; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Gingele S; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Hümmert MW; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Möhn N; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Streichert AL; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Kretschmer JR; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Grote-Levi L; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Nay S; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Seeliger T; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Ratuszny D; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Jendretzky KF; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Tkachenko D; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Jacobs R; Department of Rheumatology and Clinical Immunology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Skripuletz T; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany., Schwenkenbecher P; Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: schwenkenbecher.philipp@mh-hannover.de.
Jazyk: angličtina
Zdroj: Multiple sclerosis and related disorders [Mult Scler Relat Disord] 2024 Nov; Vol. 91, pp. 105886. Date of Electronic Publication: 2024 Sep 14.
DOI: 10.1016/j.msard.2024.105886
Abstrakt: Background: The humanized monoclonal anti-CD20-antibody ofatumumab is highly effective in treating relapsing multiple sclerosis (MS).
Objective: This study aimed to investigate the immanent effect of ofatumumab on the peripheral immune system, particularly targeting B and T cells expressing CD20.
Methods: Blood samples of 53 MS patients receiving ofatumumab were collected prior to first application and after one week, two weeks and three months. Multicolor flow cytometry was used to phenotype peripheral blood mononuclear cells, and immunoglobulin (Ig) concentrations were measured by nephelometry.
Results: Among CD20 + lymphocytes, 13 % co-expressed CD3 (identifying them as CD3 + CD20 + T lymphocytes), with a noticeable shift in the CD4/CD8-ratio towards CD8 + T cells. One week after administering ofatumumab, a significant reduction of CD20 + lymphocytes with complete depletion of CD3 + CD20 + T lymphocytes was observed, persisting during the investigation period. During the treatment, IgM levels showed a slight but significant decrease, whereas IgA and IgG levels remained stable.
Conclusion: Ofatumumab effectively depletes CD20 + lymphocytes already after the first administration. This depletion affects not only B cells, but also a small proportion of T cells (CD3 + CD20 + ), affirming the hypothesis that the anti-inflammatory effects of CD20 + cell depletion might extend to the reduction of CD3 + CD20 + T lymphocytes.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest. Outside the submitted work, some authors received honoraria for lectures, travel grants, or research grants. FFK received travel compensation from Merck, Novartis, BMS and Alexion as well as a German Research Foundation (DFG)–funded fellowship as part of the Clinician Scientist Program (PRACTIS) at Hannover Medical School. SG reports research support from Alnylam Pharmaceuticals, CSL Behring, Else Kröner Fresenius Foundation, Deutsche Forschungsgemeinschaft and Hannover Biomedical Research School (HBRS) and consulting and/or speaker honoraria from Alexion, Alnylam Pharmaceuticals, AstraZeneca, GSK, Pfizer and Merck. MWH received research support from Myelitis e. V., speaker honoraria from selpers og, Horizon and Alexion, and reimbursement of travel expenses and compensation for serving on an advisory board from Alexion. None of this interfered with the current manuscript. NM received honoraria for scientific lectures from Novartis, Merck, and Biogen as well as a German Research Foundation (DFG)–funded fellowship as part of the Clinician Scientist Program (PRACTIS) at Hannover Medical School. LGL received a German Research Foundation (DFG)–funded fellowship as part of the Clinician Scientist Program (Young Academy, Project number 413,617,135) at Hannover Medical School. SN has no conflict of interest to declare. TSe received research support from Ellen Schmidt Scholarship of the Hannover Medical School, financial support for conference attendance fees from Abbvie, and honoraria for preparation of a manuscript by Springer. DR has no conflict of interest to declare. KFJ received research support from Else Kröner Fresenius Foundation and travel compensation and congress fee from Merck and Novartis. DT has no conflict of interest to declare. ALS has no conflict of interest to declare. JRK has no conflict of interest to declare. RJ has no conflict of interest to declare. ThS reports research support from the German Ministry for Education and Research (BMBF: CurePML01EN2302), Bristol Myers Squibb Foundation for Immuno-Oncology (FA 19–010), Claudia von Schilling Foundation for Breast Cancer Research, Else Kröner Fresenius Foundation, Genzyme Neuroimmunology Fellowship, Hannover Biomedical Research School (HBRS), VHV Foundation, Alnylam Pharmaceuticals, CSL Behring, Novartis; honoraria for lectures and travel expenses for attending meetings from Alexion, Alnylam Pharmaceuticals, argenx, Bayer Vital, Biogen, Bristol Myers Squibb, Celgene, Centogene, CSL Behring, Euroimmun, Grifols, Hexal AG, Janssen-Cilag, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens, Swedish Orphan Biovitrum, Teva, Viatris; consultant fees from Alexion, Alnylam Pharmaceuticals, Biogen, Centogene, CSL Behring, Grifols, Hexal AG, Janssen-Cilag, Merck Serono, Novartis, Roche, Sanofi, Swedish Orphan Biovitrum, Viatris. PS has no conflict of interest to declare.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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