{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:49:22Z","timestamp":1787014162891,"version":"build-2736575974"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,3,27]],"date-time":"2016-03-27T00:00:00Z","timestamp":1459036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006314","name":"Biogen Idec","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006314","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>\n                      John Cunningham virus (\n                      <jats:styled-content style=\"fixed-case\">JCV<\/jats:styled-content>\n                      ) seropositivity is a risk factor for the development of natalizumab\u2010associated progressive multifocal leukoencephalopathy (\n                      <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>\n                      ) in multiple sclerosis (\n                      <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\n                      ) patients. When\n                      <jats:styled-content style=\"fixed-case\">JCV<\/jats:styled-content>\n                      seronegative patients seroconvert, their risk of developing\n                      <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>\n                      increases. Limited longitudinal data exist about the seroconversion rate amongst natalizumab\u2010treated relapsing\u2212remitting MS (\n                      <jats:styled-content style=\"fixed-case\">RRMS<\/jats:styled-content>\n                      ) patients. Our objective was to evaluate the seroconversion rate in a large Dutch cohort of natalizumab\u2010treated\n                      <jats:styled-content style=\"fixed-case\">RRMS<\/jats:styled-content>\n                      patients. Seroconversion was defined as at least two consecutive seropositive serum samples (or cessation of therapy after a single seropositive sample because of seropositivity) after initial seronegative testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      In our study of 179 patients for whom longitudinal blood samples were available over a long period (median 4.2 years), anti\u2010\n                      <jats:styled-content style=\"fixed-case\">JCV<\/jats:styled-content>\n                      antibody indices were measured in 933 available samples. Eighty\u2010six patients (48.0%) tested seronegative initially. Of these 86 seronegative patients, 23 patients (26.7%) seroconverted during follow\u2010up. The annualized seroconversion rate was 7.1%. Seroconversion occurred between 9 and 90 months (median 43 months) of treatment. The rate of seroconversion was independent of follow\u2010up duration. No significant increase was seen in the anti\u2010\n                      <jats:styled-content style=\"fixed-case\">JCV<\/jats:styled-content>\n                      antibody index in the non\u2010converting patients during the follow\u2010up.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The annualized seroconversion rate of 7.1% in patients using natalizumab, cumulatively leading to more than 25% of seronegative patients becoming seropositive in 4 years, is of clinical relevance and should be taken into account in the risk assessment when considering the start of natalizumab therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.12988","type":"journal-article","created":{"date-parts":[[2016,3,28]],"date-time":"2016-03-28T00:42:45Z","timestamp":1459125765000},"page":"1079-1085","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["High cumulative\n                    <scp>JC<\/scp>\n                    virus seroconversion rate during long\u2010term use of natalizumab"],"prefix":"10.1111","volume":"23","author":[{"given":"A.","family":"Vennegoor","sequence":"first","affiliation":[{"name":"Department of Neurology MS Centre Amsterdam VU University Medical Centre Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"van Rossum","sequence":"additional","affiliation":[{"name":"Department of Neurology MS Centre Amsterdam VU University Medical Centre Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Leurs","sequence":"additional","affiliation":[{"name":"Department of Neurology MS Centre Amsterdam VU University Medical Centre Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. P.","family":"Wattjes","sequence":"additional","affiliation":[{"name":"Department of Radiology MS Centre Amsterdam VU University Medical Centre Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Rispens","sequence":"additional","affiliation":[{"name":"Landsteiner Laboratory Sanquin Research Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. L. A. N.","family":"Murk","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology UMC Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. M. J.","family":"Uitdehaag","sequence":"additional","affiliation":[{"name":"Department of Neurology MS Centre Amsterdam VU University Medical Centre Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Killestein","sequence":"additional","affiliation":[{"name":"Department of Neurology MS Centre Amsterdam VU University Medical Centre Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117519"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044397"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107829"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511435105"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.63"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1214233"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12834"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22128"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24286"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513505353"},{"key":"e_1_2_7_12_1","unstructured":"Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 4\u22127 May 2015.Referral notification.http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/news_and_events\/news\/2015\/05\/news_detail_002323.jsp&mid=WC0b01ac058004d5c1(accessed 08\/05\/2015)"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2013.02.002"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514567728"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182583022"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-304332"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12128"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12304"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513477925"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22107"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.147.12.4178"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043335"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.03.024"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515576984"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fene.12988","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.12988","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:21:18Z","timestamp":1695550878000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.12988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,27]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1111\/ene.12988"],"URL":"https:\/\/doi.org\/10.1111\/ene.12988","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,27]]},"assertion":[{"value":"2015-09-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}