Cladribine Effects on T and B Cells and T Cell Reactivity in Multiple Sclerosis.

Autor: Holm Hansen R; Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark., von Essen MR; Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark., Mahler MR; Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark., Cobanovic S; Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark., Binko TS; Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark., Sellebjerg F; Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Annals of neurology [Ann Neurol] 2023 Sep; Vol. 94 (3), pp. 518-530. Date of Electronic Publication: 2023 May 26.
DOI: 10.1002/ana.26684
Abstrakt: 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;94:518-530.
(© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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