{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:48:32Z","timestamp":1789674512102,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T00:00:00Z","timestamp":1402358400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG 4523-A-1"],"award-info":[{"award-number":["RG 4523-A-1"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the prevalence of JC virus (JCV) reactivation and JCV\u2010specific cellular immune response during prolonged natalizumab treatment for multiple sclerosis (MS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 43 JCV\u2010seropositive MS patients, including 32 on natalizumab monotherapy &gt;18 months, 6 on interferon \u03b2\u20101a monotherapy &gt;36 months, and 5 untreated controls. We performed quantitative real\u2010time polymerase chain reaction in cerebrospinal fluid (CSF), blood, and urine for JCV DNA, and we determined JCV\u2010specific T\u2010cell responses using enzyme\u2010linked immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) assays, ex vivo and after in vitro stimulation with JCV peptides.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      JCV DNA was detected in the CSF of 2 of 27 (7.4%) natalizumab\u2010treated MS patients who had no symptoms or magnetic resonance imaging\u2013detected lesions consistent with progressive multifocal leukoencephalopathy. JCV DNA was detected in blood of 12 of 43 (27.9%) and in urine of 11 of 43 (25.6%) subjects without a difference between natalizumab\u2010treated patients and controls. JC viral load was higher in CD34\n                      <jats:sup>+<\/jats:sup>\n                      cells and in monocytes compared to other subpopulations. ICS was more sensitive than ELISpot. JCV\u2010specific T\u2010cell responses, mediated by both CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes, were detected more frequently after in vitro stimulation. JCV\u2010specific CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells were detected ex vivo more frequently in MS patients with JCV DNA in CD34\n                      <jats:sup>+<\/jats:sup>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.05) and B cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Asymptomatic JCV reactivation may occur in CSF of natalizumab\u2010treated MS patients. JCV DNA load is higher in circulating CD34\n                      <jats:sup>+<\/jats:sup>\n                      cells and monocytes compared to other mononuclear cells, and JCV in blood might trigger a JCV\u2010specific CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell response. JCV\u2010specific cellular immune response is highly prevalent in all JCV\u2010seropositive MS patients, regardless of treatment. ANN NEUROL 2014;75:925\u2013934\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24148","type":"journal-article","created":{"date-parts":[[2014,3,31]],"date-time":"2014-03-31T01:10:45Z","timestamp":1396228245000},"page":"925-934","source":"Crossref","is-referenced-by-count":46,"title":["JC virus reactivation during prolonged natalizumab monotherapy for multiple sclerosis"],"prefix":"10.1002","volume":"75","author":[{"given":"Spyridon","family":"Chalkias","sequence":"first","affiliation":[{"name":"Division of NeuroVirology Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School Boston"},{"name":"Division of Infectious Diseases Department of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Dang","sequence":"additional","affiliation":[{"name":"Division of NeuroVirology Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School Boston"},{"name":"Department of Neurology Beth Israel Deaconess Medical Center, Harvard Medical School Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Bord","sequence":"additional","affiliation":[{"name":"Division of NeuroVirology Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School Boston"},{"name":"Department of Neurology Beth Israel Deaconess Medical Center, Harvard Medical School Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion C.","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center, Harvard Medical School Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Philip","family":"Kinkel","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center, Harvard Medical School Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Sloane","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center, Harvard Medical School Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center, Harvard Medical School Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Ionete","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Massachusetts Memorial Medical Center Worcester"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria 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