{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:19:43Z","timestamp":1792685983809,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008361","name":"Scleroseforeningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008361","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Cladribine tablet therapy is an efficacious treatment for multiple sclerosis (MS), however, its mechanism of action on T and B cell subsets remains unclear. The purpose of this study was to investigate the treatment effects of cladribine on the peripheral pool of T and B cells subsets and reactivity toward central nervous system (CNS) antigens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this cross\u2010sectional exploratory study, frequencies and absolute counts of peripheral T and B cell subsets and B cell cytokine production from untreated patients with relapsing\u2013remitting MS (RRMS) and patients treated with cladribine for 1\u2009year were measured using flow cytometry. Autoreactivity was assessed using a FluoroSpot assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that 1\u2009year after initiation of cladribine treatment, a lower number of CD4<jats:sup>+<\/jats:sup> T cells was persisting whereas CD19<jats:sup>+<\/jats:sup> B cell counts were normalized compared to untreated patients with RRMS. Follicular helper T cells and their effecter subsets producing cytokines exerting distinct B cell helper activity were lower and, additionally, the peripheral B cell pool was skewed toward a na\u00efve and anti\u2010inflammatory phenotype. Finally, reactivity to the recently identified CNS\u2010enriched autoantigen RAS guanyl\u2010releasing protein 2 (RASGRP2), but not to myelin basic protein and myelin oligodendrocyte glycoprotein, was lower in cladribine\u2010treated patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Together, these investigations on T and B cell subsets suggest that cladribine treatment impairs the B\u2013T cell crosstalk and reduces their ability to mediate pathogenic effector functions. This may result in specific reduction of autoreactivity to RASGRP2 which is expressed in B cells and brain tissue. 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