CLADIN- CLADribine and INnate immune response in multiple sclerosis - A phase IV prospective study.

Cladribine Cytokines Disease activity Innate immunity Monocytes Multiple sclerosis P2X7 receptor Smouldering inflammation

Journal

Clinical immunology (Orlando, Fla.)
ISSN: 1521-7035
Titre abrégé: Clin Immunol
Pays: United States
ID NLM: 100883537

Informations de publication

Date de publication:
02 Jul 2024
Historique:
received: 26 04 2024
revised: 06 06 2024
accepted: 01 07 2024
medline: 5 7 2024
pubmed: 5 7 2024
entrez: 4 7 2024
Statut: aheadofprint

Résumé

Cladribine (Mavenclad®) is an oral treatment for relapsing remitting MS (RRMS), but its mechanism of action and its effects on innate immune responses in unknown. This study is a prospective Phase IV study of 41 patients with RRMS, and aims to investigate the mechanism of action of cladribine on peripheral monocytes, and its impact P2X7 receptor. There was a significant reduction in monocyte count in vivo at week 1 post cladribine administration, and the subset of cells being most impacted were the CD14lo CD16+ 'non-classical' monocytes. Of the 14 cytokines measured in serum, CCL2 levels increased at week 1. In vitro, cladrabine induced a reduction in P2X7R pore as well as channel activity. This study demonstrates a novel mechanism of action for cladribine. It calls for studying potential benefits of cladribine in progressive forms of MS and other neurodegenerative diseases where innate immune related inflammation is implicated in disease pathogenesis.

Identifiants

DOI: 10.1016/j.clim.2024.110304 PMID: 38964633
pubmed: 38964633
pii: S1521-6616(24)00413-3
doi: 10.1016/j.clim.2024.110304
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

110304

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest

Auteurs

Mastura Monif (M)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Melbourne Health, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia; Australian Centre for Blood diseases, Monash University, Melbourne, Australia; Department of Neurology, Eastern Health, Melbourne, VIC, Australia; Department of Physiology, The University of Melbourne, Melbourne, VIC, Australia. Electronic address: Mastura.Monif@Monash.edu.

Richard P Sequeira (RP)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia.

Andrea Muscat (A)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia.

Sian Stuckey (S)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia.

Paul G Sanfilippo (PG)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia.

Viet Minh (V)

Department of Neurology, Alfred Health, Melbourne, VIC, Australia; School of Nursing, Midwifery and Paramedicine, Australian Catholic University, Melbourne, VIC, Australia.

Naomi Loftus (N)

Department of Neurology, Alfred Health, Melbourne, VIC, Australia.

Veronica Voo (V)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia.

Katherine Fazzolari (K)

Department of Neurology, Melbourne Health, Melbourne, VIC, Australia.

Melinda Moss (M)

Department of Neurology, Alfred Health, Melbourne, VIC, Australia.

Vicki E Maltby (VE)

John Hunter Hospital, Department of Neurology, New Lambton Heights, NSW, Australia; School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.

Ai-Lan Nguyen (AL)

Department of Neurology, Melbourne Health, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.

Robb Wesselingh (R)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.

Nabil Seery (N)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.

Cassie Nesbitt (C)

Department of Neurology, Alfred Health, Melbourne, VIC, Australia; Department of Neurology, Barwon Health, Melbourne, VIC, Australia.

Josephine Baker (J)

Department of Neurology, Alfred Health, Melbourne, VIC, Australia.

Chris Dwyer (C)

Department of Neurology, Melbourne Health, Melbourne, VIC, Australia.

Lisa Taylor (L)

Department of Neurology, Melbourne Health, Melbourne, VIC, Australia.

Louise Rath (L)

Department of Neurology, Alfred Health, Melbourne, VIC, Australia.

Anneke Van der Walt (A)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.

Mark Marriott (M)

Department of Neurology, Melbourne Health, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.

Tomas Kalincik (T)

Department of Neurology, Melbourne Health, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.

Jeannette Lechner-Scott (J)

John Hunter Hospital, Department of Neurology, New Lambton Heights, NSW, Australia; School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.

Terence J O'Brien (TJ)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.

Helmut Butzkueven (H)

Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.

Classifications MeSH