Single-cell profiling reveals preferential reduction of memory B cell subsets in cladribine patients that correlates with treatment response.
cladribine
memory B cells
multiple sclerosis
Journal
Therapeutic advances in neurological disorders
ISSN: 1756-2856
Titre abrégé: Ther Adv Neurol Disord
Pays: England
ID NLM: 101480242
Informations de publication
Date de publication:
2023
2023
Historique:
received:
14
06
2023
accepted:
14
10
2023
medline:
12
12
2023
pubmed:
12
12
2023
entrez:
12
12
2023
Statut:
epublish
Résumé
Cladribine is a highly effective immunotherapy that is applied in two short-term courses over 2 years and reduces relapse rate and disease progression in patients with relapsing multiple sclerosis (MS). Despite the short treatment period, cladribine has a long-lasting effect on disease activity even after recovery of lymphocyte counts, suggesting a yet undefined long-term immune modulating effect. Our aim was to provide a more profound understanding of the detailed effects of cladribine, also with regard to the patients' therapy response. We performed an open-labeled, explorative, prospective, single-arm study, in which we examined the detailed lymphocyte subset development of MS patients who received cladribine treatment over 2 years. We performed in-depth profiling of the effects of cladribine on peripheral blood lymphocytes by flow cytometry, bulk RNA sequencing of sorted CD4 Flow cytometry revealed a predominant and sustained reduction of memory B cells compared to other B cell subsets after cladribine treatment, whereas T cell subsets were slightly reduced in a more uniform pattern. The overall transcriptional profile of total blood B cells exhibited reduced expression of proinflammatory and T cell activating genes, while single-cell transcriptomics revealed that gene expression within each B cell cluster did not change over time. Stable patients displayed stronger reductions of selected memory B cell clusters as compared to patients with clinical or cerebral MRI disease activity. We describe a pronounced and sustained effect of cladribine on the memory B cell compartment, and the resulting change in B cell subset composition causes a significant alteration of B cell transcriptional profiles resulting in reduced proinflammatory and T cell activating capacities. The extent of reduction in selected memory B cell clusters by cladribine may predict treatment response.
Sections du résumé
Background
UNASSIGNED
Cladribine is a highly effective immunotherapy that is applied in two short-term courses over 2 years and reduces relapse rate and disease progression in patients with relapsing multiple sclerosis (MS). Despite the short treatment period, cladribine has a long-lasting effect on disease activity even after recovery of lymphocyte counts, suggesting a yet undefined long-term immune modulating effect.
Objectives
UNASSIGNED
Our aim was to provide a more profound understanding of the detailed effects of cladribine, also with regard to the patients' therapy response.
Design
UNASSIGNED
We performed an open-labeled, explorative, prospective, single-arm study, in which we examined the detailed lymphocyte subset development of MS patients who received cladribine treatment over 2 years.
Methods
UNASSIGNED
We performed in-depth profiling of the effects of cladribine on peripheral blood lymphocytes by flow cytometry, bulk RNA sequencing of sorted CD4
Results
UNASSIGNED
Flow cytometry revealed a predominant and sustained reduction of memory B cells compared to other B cell subsets after cladribine treatment, whereas T cell subsets were slightly reduced in a more uniform pattern. The overall transcriptional profile of total blood B cells exhibited reduced expression of proinflammatory and T cell activating genes, while single-cell transcriptomics revealed that gene expression within each B cell cluster did not change over time. Stable patients displayed stronger reductions of selected memory B cell clusters as compared to patients with clinical or cerebral MRI disease activity.
Conclusion
UNASSIGNED
We describe a pronounced and sustained effect of cladribine on the memory B cell compartment, and the resulting change in B cell subset composition causes a significant alteration of B cell transcriptional profiles resulting in reduced proinflammatory and T cell activating capacities. The extent of reduction in selected memory B cell clusters by cladribine may predict treatment response.
Identifiants
pubmed: 38084102
doi: 10.1177/17562864231211077
pii: 10.1177_17562864231211077
pmc: PMC10710756
doi:
Types de publication
Journal Article
Langues
eng
Pagination
17562864231211077Informations de copyright
© The Author(s), 2023.
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