Comprehensive analysis of B cell repopulation in ocrelizumab-treated patients with multiple sclerosis by mass cytometry and proteomics
Ocrelizumab, an anti-CD20 antibody, depletes CD20<sup>+</sup> B cells, which subsequently repopulate over months. Little is known about changes in other immune cell populations and molecular markers associated with B cell repopulation. Here, we performed a comprehensive characterization of immune cells from ocrelizumab-treated patients with multiple sclerosis (MS) using mass cytometry. About 50% of patients showed naive B cell repopulation after 6 months mainly with a transitional phenotype, whereas CD27<sup>+</sup> memory B cells only rarely repopulated. This repopulation was associated with a reduction of memory T cells and activated myeloid cells, as well as reduced expression of activation/migration markers in both cell types. A plasma proteomics analysis identified proteins including TNFRSF13C, associated with B cell depletion and repopulation. Plasma levels of neurofilament light-chain protein declined after ocrelizumab treatment was not linked with B cell repopulation. These findings identify potential soluble markers for monitoring of ocrelizumab treatment in MS.
Authors
- Désirée Kunkel (ORCID: https://orcid.org/0000-0002-0054-955X)
- Lisa‐Marie Diekmann
- Camila Fernández‐Zapata
- Chotima Böttcher (ORCID: https://orcid.org/0000-0002-6226-586X)
- Patrick Schindler (ORCID: https://orcid.org/0000-0002-8846-121X)
- Gerardina Gallaccio
- Meng Wang (ORCID: https://orcid.org/0000-0002-0780-5608)
- Klemens Ruprecht (ORCID: https://orcid.org/0000-0003-1962-6014)
- Péter Körtvelyessy (ORCID: https://orcid.org/0000-0003-1262-6169)
- Adeline Dehlinger (ORCID: https://orcid.org/0000-0001-6611-114X)
- Friedemann Paul (ORCID: https://orcid.org/0000-0002-6378-0070)
- Carolin Otto (ORCID: https://orcid.org/0000-0002-9768-5143)
- Moritz Niederschweiberer (ORCID: https://orcid.org/0000-0002-0234-1701)
Institutions
- Max Delbrück Center (DE)
- Humboldt-Universität zu Berlin (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- iScience
- Published
- 2025-04-08
- DOI
- https://doi.org/10.1016/j.isci.2025.112383
- Citations
- 4
- Primary Topic
- Multiple Sclerosis Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 5.89
Funders
- Deutsche Forschungsgemeinschaft
- National Natural Science Foundation of China
- Bundesministerium für Bildung und Forschung
- Government of Jiangsu Province
- China Scholarship Council
- Natural Science Foundation of Jiangsu Province
- Medical Research Council
- National Medical Research Council