Cladribine Effects on T and B Cells and T Cell Reactivity in Multiple Sclerosis.
Ann Neurol
; 94(3): 518-530, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37191113
ABSTRACT
OBJECTIVE:
Cladribine tablet therapy is an efficacious treatment for multiple sclerosis (MS), however, its mechanism of action on T and B cell subsets remains unclear. The purpose of this study was to investigate the treatment effects of cladribine on the peripheral pool of T and B cells subsets and reactivity toward central nervous system (CNS) antigens.METHODS:
In this cross-sectional exploratory study, frequencies and absolute counts of peripheral T and B cell subsets and B cell cytokine production from untreated patients with relapsing-remitting MS (RRMS) and patients treated with cladribine for 1 year were measured using flow cytometry. Autoreactivity was assessed using a FluoroSpot assay.RESULTS:
We found that 1 year after initiation of cladribine treatment, a lower number of CD4+ T cells was persisting whereas CD19+ B cell counts were normalized compared to untreated patients with RRMS. Follicular helper T cells and their effecter subsets producing cytokines exerting distinct B cell helper activity were lower and, additionally, the peripheral B cell pool was skewed toward a naïve and anti-inflammatory phenotype. Finally, reactivity to the recently identified CNS-enriched autoantigen RAS guanyl-releasing protein 2 (RASGRP2), but not to myelin basic protein and myelin oligodendrocyte glycoprotein, was lower in cladribine-treated patients.INTERPRETATION:
Together, these investigations on T and B cell subsets suggest that cladribine treatment impairs the B-T cell crosstalk and reduces their ability to mediate pathogenic effector functions. This may result in specific reduction of autoreactivity to RASGRP2 which is expressed in B cells and brain tissue. ANN NEUROL 2023;94518-530.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cladribina
/
Esclerose Múltipla
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Ann Neurol
Ano de publicação:
2023
Tipo de documento:
Article