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

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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.

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.

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.

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
TidsskriftAnnals of Neurology
Udgave nummer3
Sider (fra-til)518-530
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The authors highly acknowledge Lisbeth Stolpe for her excellent technical assistance. This study was financially supported by Merck A/S, Soborg, Denmark, an affiliate of Merck KGaA Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945), however, Merck had no influence on the conduct, analysis, or interpretation of data. Finn Sellebjerg holds a professorship funded by the Danish Multiple Sclerosis Society.

Publisher Copyright:
© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

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