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

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2024-07-02 DOI:10.1016/j.clim.2024.110304

Mastura Monif , Richard P. Sequeira , Andrea Muscat , Sian Stuckey , Paul G. Sanfilippo , Viet Minh , Naomi Loftus , Veronica Voo , Katherine Fazzolari , Melinda Moss , Vicki E. Maltby , Ai-Lan Nguyen , Robb Wesselingh , Nabil Seery , Cassie Nesbitt , Josephine Baker , Chris Dwyer , Lisa Taylor , Louise Rath , Anneke Van der Walt , Helmut Butzkueven

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引用次数: 0

Abstract

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 on the 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.

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多发性硬化症中的 CLADIN- CLADribine 和 INnate 免疫反应--一项 IV 期前瞻性研究。

克拉利宾（Mavenclad®）是一种治疗复发性缓解型多发性硬化症（RRMS）的口服药物，但其作用机制及其对先天性免疫反应的影响尚不清楚。本研究是一项前瞻性 IV 期研究，对 41 名 RRMS 患者进行了研究，旨在探讨克拉利宾对外周单核细胞的作用机制及其对 P2X7 受体的影响。服用克拉利宾一周后，体内单核细胞数量明显减少，受影响最大的细胞亚群是 CD14lo CD16+"非典型 "单核细胞。在血清中测量的 14 种细胞因子中，CCL2 的水平在第 1 周时有所增加。在体外，克拉拉滨可降低 P2X7R 孔隙和通道活性。这项研究证明了克拉利宾的新作用机制。它呼吁研究克拉利宾对进行性多发性硬化症和其他神经退行性疾病的潜在益处，因为先天性免疫相关炎症与疾病的发病机制有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.