{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:42:01Z","timestamp":1788385321444,"version":"build-2803163510"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>B cells are acknowledged as crucial players in the pathogenesis of multiple sclerosis (MS). Several disease modifying drugs including cladribine have been shown to exert differential effects on peripheral blood B cell subsets. However, little is known regarding functional changes within the peripheral B cell populations. In this study, we obtained a detailed picture of B cell repertoire changes under cladribine treatment on a combined immunoglobulin (Ig) transcriptome and proteome level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed next-generation sequencing of Ig heavy chain (IGH) transcripts and Ig mass spectrometry in cladribine-treated patients with relapsing-remitting multiple sclerosis (n = 8) at baseline and after 6 and 12 months of treatment in order to generate Ig transcriptome and Ig peptide libraries. Ig peptides were overlapped with the corresponding IGH transcriptome in order to analyze B cell clones on a combined transcriptome and proteome level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The analysis of peripheral blood B cell percentages pointed towards a significant decrease of memory B cells and an increase of naive B cells following cladribine therapy. While basic IGH repertoire parameters (e.g. variable heavy chain family usage and Ig subclasses) were only slightly affected by cladribine treatment, a significantly decreased number of clones and significantly lower diversity in the memory subset was noticeable at 6 months following treatment which was sustained at 12 months. When looking at B-cell clones comprising sequences from the different time-points, clones spanning between all three time-points were significantly more frequent than clones including sequences from two time-points. Furthermore, Ig proteome analyses showed that Ig transcriptome specific peptides could mostly be equally aligned to all three time-points pointing towards a proportion of B-cell clones that are maintained during treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings suggest that peripheral B cell related treatment effects of cladribine tablets might be exerted through a reduction of possibly disease relevant clones in the memory B cell subset without disrupting the overall clonal composition of B cells. Our results -at least partially- might explain the relatively mild side effects regarding infections and the sustained immune response after vaccinations during treatment. However, exact disease driving B cell subsets and their effects remain unknown and should be addressed in future studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1133967","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T06:17:16Z","timestamp":1678169836000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Cladribine treatment specifically affects peripheral blood memory B cell clones and clonal expansion in multiple sclerosis patients"],"prefix":"10.3389","volume":"14","author":[{"given":"Christoph","family":"Ruschil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Gabernet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze 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