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All 33 pwMS were examined longitudinally at baseline and six months after treatment with ozanimod, fingolimod, dimethyl fumarate, teriflunomide, cladribine or natalizumab. Ig peptides were obtained longitudinally in a subset of treated pwMS by Ig mass spectrometry, overlapped with VH transcriptomes through nf-core bioinformatics workflow analysis and additionally Ig serum level and anti-Epstein-Barr virus IgG level (EBNA1) were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>VH repertoires of treatment-na\u00efve pwMS showed a significantly decreased diversity in the double negative B cells and different usage of IGHV genes when compared with healthy controls. Quantitative changes in B cell subsets during treatment were accompanied by qualitative changes in Ig repertoires with a significantly decreased diversity in the naive, memory B cells and plasmablasts during ozanimod treatment. A similar trend was noticeable for all other treatments except natalizumab. No qualitative change in Ig peptides overlapping with Ig transcriptome repertoires was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides first evidence for an altered peripheral Ig repertoire in pwMS. In addition, various treatments seem to shift the composition of B cells towards an increased fraction and activation of the naive B cell pool and a reduced fraction of memory B cells with reduced clonal diversity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-026-03735-0","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T07:14:10Z","timestamp":1776150850000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extensive peripheral immunoglobulin repertoire analyses in people with multiple sclerosis reveal disease-specific signatures and distinct treatment effects of disease modifying drugs"],"prefix":"10.1186","volume":"23","author":[{"given":"Nicole","family":"Vasilenko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Ruschil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josua","family":"Stadelmaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria P.","family":"Tieck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Schembecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory P.","family":"Owens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Berthele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Ziemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Poli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Snaidero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Nahnsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Jarboui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Bichmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Gabernet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus C.","family":"Kowarik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"3735_CR1","doi-asserted-by":"publisher","first-page":"175628642110076","DOI":"10.1177\/17562864211007687","volume":"14","author":"S Haase","year":"2021","unstructured":"Haase S, Linker RA. 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The study was approved by the local ethics committee of the Eberhard Karls University of T\u00fcbingen (No. 204\/2018BO2), and previously approved by the ethics committees of the other clinics [\n                      \n                      ,\n                      \n                      ,\n                      \n                      ].","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"128"}}