Effects of cladribine on intrathecal and peripheral B and plasma cells.

Autor:	Allen-Philbey K; Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK.; Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK., Stephenson S; Division of Haematology and Immunology, Leeds Institute of Medical Research, University of Leeds, Leeds, UK., Doody G; Division of Haematology and Immunology, Leeds Institute of Medical Research, University of Leeds, Leeds, UK., MacDougall A; London School of Hygiene & Tropical Medicine, Department of Medical Statistics., Aboulwafaali M; Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK.; Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK., Ammoscato F; Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK., Andrews M; Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK., Gnanapavan S; Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK.; Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK., Giovannoni G; Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK.; Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.; Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK., Grigoriadou S; Department of Immunology, The Royal London Hospital, Barts Health NHS Trust, London, UK., Hickey A; Department of Immunology, The Royal London Hospital, Barts Health NHS Trust, London, UK., Holden DW; Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK.; Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK., Lock H; Department of Immunology, The Royal London Hospital, Barts Health NHS Trust, London, UK., Papachatzaki M; Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK., Redha I; Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.; Khawlah Hospital, Ministry of Health, Oman., Baker D; Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK., Tooze R; Division of Haematology and Immunology, Leeds Institute of Medical Research, University of Leeds, Leeds, UK., Schmierer K; Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK.; Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Jazyk:	angličtina
Zdroj:	Clinical and experimental immunology [Clin Exp Immunol] 2024 Dec 12. Date of Electronic Publication: 2024 Dec 12.
DOI:	10.1093/cei/uxae116
Abstrakt:	Introduction: Cladribine is a deoxyadenosine analogue that can penetrate the blood-brain barrier. It is used to treat multiple sclerosis (MS). However, the mechanistic understanding of the effect of this highly effective therapy on B cells and plasma cells in the central nervous system compartment is limited. The CLADRIPLAS study examined the effect of cladribine on peripheral and intrathecal B and plasma cell biology in people with MS. Methods: Thirty-eight people with progressive MS ineligible for- or rejecting- treatment with licenced therapies were recruited and supplied a baseline lumbar puncture. Those exhibiting gadolinium-enhancing or new/enlarging T2 magnetic resonance imaging lesions and/or elevated neurofilament levels were offered subcutaneous cladribine (Litak®). Seven people were eligible; one person died before treatment, and only five completed the first year of treatment. Twenty-two ineligible people were willing to provide a repeat lumbar puncture twelve months later. Results: The CLADRIPLAS study found no evidence of a difference in the odds of a positive cerebrospinal fluid oligoclonal band (cOCB) result between the cladribine-treated and untreated group. This is probably explained by microarray and in vitro studies, which demonstrated that plasmablasts and notably long-lived plasma cells are relatively resistant to the cytotoxic effect of cladribine compared to memory B cells at physiological concentrations. This was consistent with the loss of intracellular deoxycytidine kinase during antibody-secreting cell differentiation. Conclusion: CLADRIPLAS indicates that cOCB are not rapidly eliminated in most people with MS. This may be explained by the relative lack of direct cytotoxic action of cladribine on long-lived plasma cells. (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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