Sustained effects on immune cell subsets and autoreactivity in multiple sclerosis patients treated with oral cladribine

Rikke Holm Hansen, Marina Rode von Essen, Mie Reith Mahler, Stefan Cobanovic, Finn Sellebjerg

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Abstract

INTRODUCTION: Cladribine tablet therapy is an efficacious treatment for multiple sclerosis (MS). Recently, we showed that one year after the initiation of cladribine treatment, T and B cell crosstalk was impaired, reducing potentially pathogenic effector functions along with a specific reduction of autoreactivity to RAS guanyl releasing protein 2 (RASGRP2). In the present study we conducted a longitudinal analysis of the effect of cladribine treatment in patients with RRMS, focusing on the extent to which the effects observed on T and B cell subsets and autoreactivity after one year of treatment are maintained, modulated, or amplified during the second year of treatment.

METHODS: In this case-control 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 52 (W52), 60 (W60), 72 (W72) and 96 (W96) weeks, were measured using flow cytometry. Autoreactivity was assessed using a FluoroSpot assay.

RESULTS: We found a substantial reduction in circulating memory B cells and proinflammatory B cell responses. Furthermore, we observed reduced T cell responses to autoantigens possibly presented by B cells (RASGRP2 and a-B crystallin (CRYAB)) at W52 and W96 and a further reduction in responses to the myelin antigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) after 96 weeks.

CONCLUSION: We conclude that the effects of cladribine observed after year one are maintained and, for some effects, even increased two years after the initiation of a full course of treatment with cladribine tablets.

Original languageEnglish
Article number1327672
JournalFrontiers in Immunology
Volume15
Number of pages13
ISSN1664-3224
DOIs
Publication statusPublished - 2024

Bibliographical note

Copyright © 2024 Holm Hansen, von Essen, Reith Mahler, Cobanovic and Sellebjerg.

Keywords

  • Humans
  • Multiple Sclerosis/drug therapy
  • Cladribine/therapeutic use
  • Multiple Sclerosis, Relapsing-Remitting/drug therapy
  • Myelin-Oligodendrocyte Glycoprotein
  • B-Lymphocyte Subsets
  • Guanine Nucleotide Exchange Factors

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