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PML occurs preferentially in patients with compromised immune system, but has been also observed in multiple sclerosis (MS) patients treated with disease-modifying drugs. We characterized T and B cells in 5 MS patients that developed PML, 4 during natalizumab therapy and one after alemtuzumab treatment, and in treated patients who did not develop the disease. Results revealed that: i) thymic and bone marrow output was impaired in 4 out 5 patients at the time of PML development; ii) T-cell repertoire was restricted; iii) clonally expanded T cells were present in all patients. However, common usage or pairings of T-cell receptor beta variable or joining genes, specific clonotypes or obvious \u201cpublic\u201d T-cell response were not detected at the moment of PML onset. Similarly, common restrictions were not found in the immunoglobulin heavy chain repertoire. The data indicate that no JCV-related specific T- and B-cell expansions were mounted at the time of PML. The current results enhance our understanding of JC virus infection and PML, and should be taken into account when choosing targeted therapies.<\/jats:p>","DOI":"10.1038\/s41598-019-53010-x","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T11:03:18Z","timestamp":1573556598000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lack of specific T- and B-cell clonal expansions in multiple sclerosis patients with progressive multifocal leukoencephalopathy"],"prefix":"10.1038","volume":"9","author":[{"given":"Diego","family":"Bertoli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Sottini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruggero","family":"Capra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Scarpazza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7881-7550","authenticated-orcid":false,"given":"Roberto","family":"Bresciani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8335-0262","authenticated-orcid":false,"given":"Luigi D.","family":"Notarangelo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Imberti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,11,12]]},"reference":[{"key":"53010_CR1","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.3389\/fimmu.2017.01646","volume":"8","author":"Y Taoufik","year":"2017","unstructured":"Taoufik, Y. & de Go\u00ebr de Herve, M. 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BMC Bioinformatics. 15, 7, https:\/\/doi.org\/10.1186\/1471-2105-15-7 (2014).","journal-title":"BMC Bioinformatics."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53010-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53010-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53010-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T15:55:19Z","timestamp":1671292519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53010-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,12]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["53010"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-53010-x","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,12]]},"assertion":[{"value":"20 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"D.B., A.S., C.S., R.B. and L.D.N. authors declare no competing interests. R.C. has received lecture fees and\/or travel grants from Novartis, Biogen, Celgene, Novartis, TEVA, Genzyme and Sanofi-Aventis. L.I. has received speaker honoraria from Biogen Idec, Meck-Serono, Novartis and Genzyme-Sanofi and has participated to scientific advisory board for Biogen Idec. She has received research funding from FISM (Fondazione Italiana Sclerosi Multipla) and research support from Meck-Serono and Genzyme-Sanofi.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16605"}}