ORIGINAL RESEARCH article
Front. Immunol.
Sec. B Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1590165
B cell-extrinsic and intrinsic factors linked to early immune repletion after anti-CD20 therapy in patients with Multiple Sclerosis of African Ancestry
Provisionally accepted
Gregg Joshua Silverman*
Abhimanyu Amarnani
Arnaldo A Armini
Angie KimHannah KopinskyDavid Fenyo
Ilya Kister- Grossman School of Medicine, New York University, New York, New York, United States
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In recent investigations, we identified patients of African ancestry (AA) with Multiple Sclerosis(MS) who, after treatment with an anti-CD20 monoclonal antibody, display more rapid B-cell repopulation after semi-annual infusions. In this study, we explored immunologic, serum drug monitoring, and genetic factors that may contribute to this faster rate of B-cell repletion. Our assessment of extrinsic factors revealed an unexpected prevalence of anti-drug antibodies against ocrelizumab with concurrent undetectable serum drug levels in this patient subset. From considerations of intrinsic factors, a separate set of ER patients of African descent, without anti-drug antibodies, showed a significant overrepresentation of genetic polymorphisms that map to genes for the B cell survival factor (BAFF) and antibody-dependent cytotoxicity, as well as pathways involved in the inflammatory response, leukocyte activation, and B cell differentiation. Larger studies are now needed to determine whether these genetic factors in AA MS patients, associated with early repletion, may lead to impaired therapeutic benefits and clinical progression, and these findings may be useful to guide future personalized therapeutic strategies.
Keywords: Ocrelizumab, Multiple Sclerosis, rituximab, CD20, African ancestry, B-cell repletion, Genetics, B-Cell Activating Factor
Received: 08 Mar 2025; Accepted: 22 Apr 2025.
Copyright: © 2025 Silverman, Amarnani, Armini, Kim, Kopinsky, Fenyo and Kister. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Gregg Joshua Silverman, Grossman School of Medicine, New York University, New York, 10016, New York, United States
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