{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:26:55Z","timestamp":1790681215015,"version":"4.1.0"},"reference-count":35,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"vor","delay-in-days":959,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY022936"],"award-info":[{"award-number":["R01EY022936"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DFG","award":["EXC 2145 SyNergy"],"award-info":[{"award-number":["EXC 2145 SyNergy"]}]},{"name":"DFG","award":["Ko 4367\/1-1"],"award-info":[{"award-number":["Ko 4367\/1-1"]}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","award":["Independent Research Grant"],"award-info":[{"award-number":["Independent Research Grant"]}],"id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["neurotherapeuticsjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurotherapeutics"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1007\/s13311-020-00975-7","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T13:04:15Z","timestamp":1606741455000},"page":"364-377","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":36,"title":["Differential Effects of Fingolimod and Natalizumab on B Cell Repertoires in Multiple Sclerosis Patients"],"prefix":"10.1016","volume":"18","author":[{"given":"M.C.","family":"Kowarik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Astling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Lepennetier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ritchie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Hemmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.P.","family":"Owens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-1394","authenticated-orcid":false,"given":"Jeffrey L.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1007\/s13311-020-00975-7_bib1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00281-014-0424-x","article-title":"B cells in MS and NMO: pathogenesis and therapy","volume":"36","author":"Krumbholz","year":"2014","journal-title":"Semin Immunopathol."},{"issue":"7","key":"10.1007\/s13311-020-00975-7_bib2","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1001\/jamaneurol.2019.0905","article-title":"Association of intrathecal immunoglobulin G synthesis with disability worsening in multiple sclerosis","volume":"76","author":"Gasperi","year":"2019","journal-title":"JAMA Neurol."},{"key":"10.1007\/s13311-020-00975-7_bib3","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1016\/S0140-6736(11)61649-8","article-title":"Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial","volume":"378","author":"Kappos","year":"2011","journal-title":"Lancet."},{"issue":"3","key":"10.1007\/s13311-020-00975-7_bib4","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1056\/NEJMoa1606468","article-title":"Ocrelizumab versus placebo in primary progressive multiple sclerosis","volume":"376","author":"Montalban","year":"2017","journal-title":"N Engl J Med."},{"issue":"3","key":"10.1007\/s13311-020-00975-7_bib5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1056\/NEJMoa1601277","article-title":"Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis","volume":"376","author":"Hauser","year":"2017","journal-title":"N Engl J Med."},{"key":"10.1007\/s13311-020-00975-7_bib6","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJMoa0909494","article-title":"A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis","volume":"362","author":"Kappos","year":"2010","journal-title":"N Engl J Med."},{"key":"10.1007\/s13311-020-00975-7_bib7","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1056\/NEJMoa044397","article-title":"A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis","volume":"354","author":"Polman","year":"2006","journal-title":"N Engl J Med."},{"key":"10.1007\/s13311-020-00975-7_bib8","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1126\/science.1070238","article-title":"Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists","volume":"296","author":"Mandala","year":"2002","journal-title":"Science."},{"key":"10.1007\/s13311-020-00975-7_bib9","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature02284","article-title":"Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1","volume":"427","author":"Matloubian","year":"2004","journal-title":"Nature."},{"key":"10.1007\/s13311-020-00975-7_bib10","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1212\/WNL.0b013e3182143564","article-title":"Differential effects of fingolimod (FTY720) on immune cells in the CSF and blood of patients with MS","volume":"76","author":"Kowarik","year":"2011","journal-title":"Neurology."},{"key":"10.1007\/s13311-020-00975-7_bib11","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/ana.20858","article-title":"Immune surveillance in multiple sclerosis patients treated with natalizumab","volume":"59","author":"Stuve","year":"2006","journal-title":"Ann Neurol."},{"issue":"5580","key":"10.1007\/s13311-020-00975-7_bib12","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.1071632","article-title":"Integrin-mediated long-term B cell retention in the splenic marginal zone","volume":"297","author":"Lu","year":"2002","journal-title":"Science."},{"key":"10.1007\/s13311-020-00975-7_bib13","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/acn3.418","article-title":"CNS aquaporin-4-specific B cells connect with multiple B-cell compartments in neuromyelitis optica spectrum disorder","volume":"4","author":"Kowarik","year":"2017","journal-title":"Ann Clin Transl Neurol."},{"key":"10.1007\/s13311-020-00975-7_bib14","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nmeth.1778","article-title":"Counting absolute numbers of molecules using unique molecular identifiers","volume":"9","author":"Kivioja","year":"2012","journal-title":"Nature methods."},{"key":"10.1007\/s13311-020-00975-7_bib15","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1093\/bioinformatics\/btu138","article-title":"pRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires","volume":"30","author":"Van der Heiden","year":"2014","journal-title":"Bioinformatics."},{"key":"10.1007\/s13311-020-00975-7_bib16","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/978-1-61779-842-9_32","article-title":"IMGT((R)) tools for the nucleotide analysis of immunoglobulin (IG) and T cell receptor (TR) V-(D)-J repertoires, polymorphisms, and IG mutations: IMGT\/V-QUEST and IMGT\/HighV-QUEST for NGS","volume":"882","author":"Alamyar","year":"2012","journal-title":"Methods Mol Biol."},{"issue":"1-2","key":"10.1007\/s13311-020-00975-7_bib17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jim.2008.06.006","article-title":"IgTree: creating immunoglobulin variable region gene lineage trees","volume":"338","author":"Barak","year":"2008","journal-title":"J Immunol Methods."},{"key":"10.1007\/s13311-020-00975-7_bib18","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1172\/JCI119433","article-title":"Analysis of the human VH gene repertoire","volume":"99","author":"Brezinschek","year":"1998","journal-title":"J. Clin. Invest."},{"issue":"9","key":"10.1007\/s13311-020-00975-7_bib19","doi-asserted-by":"crossref","first-page":"6343","DOI":"10.4049\/jimmunol.179.9.6343","article-title":"VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis","volume":"179","author":"Owens","year":"2007","journal-title":"J Immunol."},{"issue":"1","key":"10.1007\/s13311-020-00975-7_bib20","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s12974-019-1593-2","article-title":"Natalizumab promotes activation and pro-inflammatory differentiation of peripheral B cells in multiple sclerosis patients","volume":"16","author":"Traub","year":"2019","journal-title":"J Neuroinflammation."},{"key":"10.1007\/s13311-020-00975-7_bib21","unstructured":"Kemmerer CL, Pernpeintner V, Ruschil C et al. Differential effects of disease modifying drugs on peripheral blood B cell subsets: a cross sectional study in multiple sclerosis patients treated with interferon-\u03b2, glatiramer acetate, dimethyl fumarate, fingolimod or natalizumab. PlosOne. In press."},{"issue":"12","key":"10.1007\/s13311-020-00975-7_bib22","doi-asserted-by":"crossref","first-page":"4533","DOI":"10.1172\/JCI63842","article-title":"B cell exchange across the blood-brain barrier in multiple sclerosis","volume":"122","author":"von B\u00fcdingen","year":"2012","journal-title":"J Clin Invest."},{"issue":"248","key":"10.1007\/s13311-020-00975-7_bib23","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3008930","article-title":"Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis","volume":"6","author":"Palanichamy","year":"2014","journal-title":"Sci Transl Med"},{"issue":"248","key":"10.1007\/s13311-020-00975-7_bib24","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3008879","article-title":"B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes","volume":"6","author":"Stern","year":"2014","journal-title":"Sci Transl Med"},{"issue":"2","key":"10.1007\/s13311-020-00975-7_bib25","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1750-3639.2004.tb00049.x","article-title":"Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis","volume":"14","author":"Serafini","year":"2004","journal-title":"Brain Pathol."},{"key":"10.1007\/s13311-020-00975-7_bib26","doi-asserted-by":"crossref","unstructured":"Greenfield AL, Dandekar R, Ramesh A, et al. Longitudinally persistent cerebrospinal fluid B cells can resist treatment in multiple sclerosis. JCI Insight. 2019;4(6).","DOI":"10.1172\/jci.insight.126599"},{"issue":"3","key":"10.1007\/s13311-020-00975-7_bib27","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/cei.12590","article-title":"High interindividual variability in the CD4\/CD8 T cell ratio and natalizumab concentration levels in the cerebrospinal fluid of patients with multiple sclerosis","volume":"180","author":"Harrer","year":"2015","journal-title":"Clin Exp Immunol."},{"issue":"5","key":"10.1007\/s13311-020-00975-7_bib28","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/ana.24387","article-title":"B-cell very late antigen-4 deficiency reduces leukocyte recruitment and susceptibility to central nervous system autoimmunity","volume":"77","author":"Lehmann-Horn","year":"2015","journal-title":"Ann Neurol."},{"issue":"10","key":"10.1007\/s13311-020-00975-7_bib29","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1007\/s12272-010-1008-5","article-title":"Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (fingolimod) in multiple sclerosis","volume":"33","author":"Lee","year":"2010","journal-title":"Arch Pharm Res."},{"key":"10.1007\/s13311-020-00975-7_bib30","doi-asserted-by":"crossref","unstructured":"Rothhammer V, Kenison JE, Tjon E, et al. Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation. Proc Natl Acad Sci U S A. 2017 Feb 6.","DOI":"10.1073\/pnas.1615413114"},{"key":"10.1007\/s13311-020-00975-7_bib31","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1073\/pnas.1014154108","article-title":"FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation","volume":"108","author":"Choi","year":"2011","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"13","key":"10.1007\/s13311-020-00975-7_bib32","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.1182\/blood-2004-06-2075","article-title":"FTY720 suppresses humoral immunity by inhibiting germinal center reaction","volume":"104","author":"Han","year":"2004","journal-title":"Blood."},{"issue":"7","key":"10.1007\/s13311-020-00975-7_bib33","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/ni.3175","article-title":"Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus","volume":"16","author":"Tipton","year":"2015","journal-title":"Nat Immunol."},{"issue":"10023","key":"10.1007\/s13311-020-00975-7_bib34","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S0140-6736(15)01314-8","article-title":"Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial","volume":"387","author":"Lublin","year":"2016","journal-title":"Lancet."},{"issue":"10127","key":"10.1007\/s13311-020-00975-7_bib35","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0140-6736(18)30475-6","article-title":"Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study","volume":"391","author":"Kappos","year":"2018","journal-title":"Lancet."}],"container-title":["Neurotherapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13311-020-00975-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13311-020-00975-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747923012023?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747923012023?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13311-020-00975-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:54:28Z","timestamp":1761807268000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1878747923012023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["S1878747923012023"],"URL":"https:\/\/doi.org\/10.1007\/s13311-020-00975-7","relation":{},"ISSN":["1878-7479"],"issn-type":[{"value":"1878-7479","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Differential Effects of Fingolimod and Natalizumab on B Cell Repertoires in Multiple Sclerosis Patients","name":"articletitle","label":"Article Title"},{"value":"Neurotherapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1007\/s13311-020-00975-7","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2021 The American Society for Experimental NeuroTherapeutics, Inc. Published by Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}