Extended interval dosing of ocrelizumab modifies the repopulation of B cells without altering the clinical efficacy in multiple sclerosis.
B cells
Multiple sclerosis
Ocrelizumab
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
26 Sep 2023
26 Sep 2023
Historique:
received:
19
07
2023
accepted:
19
09
2023
medline:
4
10
2023
pubmed:
27
9
2023
entrez:
26
9
2023
Statut:
epublish
Résumé
Recent studies suggest that extended interval dosing of ocrelizumab, an anti-B cell therapy, does not affect its clinical effectiveness in most patients with multiple sclerosis (MS). However, it remains to be established whether certain B cell subsets are differentially repopulated after different dosing intervals and whether these subsets relate to clinical efficacy. We performed high-dimensional single-cell characterization of the peripheral immune landscape of patients with MS after standard (SID; n = 43) or extended interval dosing (EID; n = 37) of ocrelizumab and in non-ocrelizumab-treated (control group, CG; n = 28) patients with MS, using mass cytometry by time of flight (CyTOF). The first B cells that repopulate after both ocrelizumab dosing schemes were immature, transitional and regulatory CD1d Taken together, our data highlight that extending the dosing interval of ocrelizumab does not lead to increased repopulation of effector B cells. We show that the increase of CD20 expression on B cell subsets in EID might lead to longer depletion or less repopulation of B cells after the next infusion of ocrelizumab. Lastly, even though extending the ocrelizumab interval dosing alters B cell repopulation, it does not affect the clinical efficacy of ocrelizumab in our cohort of patients with MS.
Sections du résumé
BACKGROUND
BACKGROUND
Recent studies suggest that extended interval dosing of ocrelizumab, an anti-B cell therapy, does not affect its clinical effectiveness in most patients with multiple sclerosis (MS). However, it remains to be established whether certain B cell subsets are differentially repopulated after different dosing intervals and whether these subsets relate to clinical efficacy.
METHODS
METHODS
We performed high-dimensional single-cell characterization of the peripheral immune landscape of patients with MS after standard (SID; n = 43) or extended interval dosing (EID; n = 37) of ocrelizumab and in non-ocrelizumab-treated (control group, CG; n = 28) patients with MS, using mass cytometry by time of flight (CyTOF).
RESULTS
RESULTS
The first B cells that repopulate after both ocrelizumab dosing schemes were immature, transitional and regulatory CD1d
CONCLUSIONS
CONCLUSIONS
Taken together, our data highlight that extending the dosing interval of ocrelizumab does not lead to increased repopulation of effector B cells. We show that the increase of CD20 expression on B cell subsets in EID might lead to longer depletion or less repopulation of B cells after the next infusion of ocrelizumab. Lastly, even though extending the ocrelizumab interval dosing alters B cell repopulation, it does not affect the clinical efficacy of ocrelizumab in our cohort of patients with MS.
Identifiants
pubmed: 37752582
doi: 10.1186/s12974-023-02900-z
pii: 10.1186/s12974-023-02900-z
pmc: PMC10521424
doi:
Substances chimiques
ocrelizumab
A10SJL62JY
Antibodies, Monoclonal, Humanized
0
Immunologic Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
215Subventions
Organisme : Stichting MS Research
ID : MS18-358
Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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