{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:47:00Z","timestamp":1787064420870,"version":"build-2736575974"},"reference-count":113,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,22]],"date-time":"2025-06-22T00:00:00Z","timestamp":1750550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pediatric-onset multiple sclerosis (POMS) is a rare yet increasingly recognized demyelinating disease of the central nervous system, characterized by a highly inflammatory disease course and an elevated relapse rate compared to adult-onset MS (AOMS). Given the unique immunopathogenesis of POMS, recent therapeutic strategies have shifted toward early initiation of high-efficacy disease-modifying therapies (DMTs) to minimize irreversible neurological damage. Among these, B-cell-targeting therapies, particularly anti-CD20 monoclonal antibodies, have shown efficacy in adult MS and are emerging as promising candidates for POMS treatment. The present review summarizes the current knowledge of the role of B-cells in POMS pathophysiology and evaluates the therapeutic potential of anti-CD-20 agents. It also highlights ongoing clinical trials and future perspectives, including novel B-cell-directed approaches such as anti-CD19 therapies, Bruton\u2019s tyrosine kinase (BTK) inhibitors, and BAFF-targeting agents.<\/jats:p>","DOI":"10.3390\/ijms26135989","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T09:08:44Z","timestamp":1750669724000},"page":"5989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Advancing Treatment in Pediatric Multiple Sclerosis: The Promise of B-Cell-Targeting Therapies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1781-2799","authenticated-orcid":false,"given":"Charalampos","family":"Skarlis","sequence":"first","affiliation":[{"name":"Research Immunogenetics Laboratory, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kotsari","sequence":"additional","affiliation":[{"name":"Research Immunogenetics Laboratory, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8934-670X","authenticated-orcid":false,"given":"Maria","family":"Anagnostouli","sequence":"additional","affiliation":[{"name":"Research Immunogenetics Laboratory, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"},{"name":"Multiple Sclerosis and Demyelinating Diseases Unit, Center of Expertise for Rare Demyelinating and Autoimmune Diseases of CNS, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Aeginition University Hospital, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,22]]},"reference":[{"key":"ref_1","first-page":"793","article-title":"Pediatric Central Nervous System Demyelinating Diseases","volume":"25","author":"Chitnis","year":"2019","journal-title":"Continuum"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nrneurol.2009.158","article-title":"Pediatric Multiple Sclerosis","volume":"5","author":"Yeh","year":"2009","journal-title":"Nat. Rev. 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