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 language | English |
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Article number | 1327672 |
Journal | Frontiers in Immunology |
Volume | 15 |
Number of pages | 13 |
ISSN | 1664-3224 |
DOIs | |
Publication status | Published - 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