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
{"title":"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。","authors":"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","doi":"10.1016/j.clim.2024.110304","DOIUrl":null,"url":null,"abstract":"<div><p>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 <em>in vivo</em> 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. <em>In vitro</em>, 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.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110304"},"PeriodicalIF":4.5000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CLADIN- CLADribine and INnate immune response in multiple sclerosis – A phase IV prospective study\",\"authors\":\"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\",\"doi\":\"10.1016/j.clim.2024.110304\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 <em>in vivo</em> 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. <em>In vitro</em>, 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.</p></div>\",\"PeriodicalId\":10392,\"journal\":{\"name\":\"Clinical immunology\",\"volume\":\"265 \",\"pages\":\"Article 110304\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-07-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1521661624004133\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521661624004133","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
CLADIN- CLADribine and INnate immune response in multiple sclerosis – A phase IV prospective study
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.
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.
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