{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:49:06Z","timestamp":1789674546974,"version":"4.0.1"},"reference-count":27,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2015,10,2]],"date-time":"2015-10-02T00:00:00Z","timestamp":1443744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Natalizumab treatment is associated with progressive multifocal leukoencephalopathy (PML) development. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for risk stratification, but PML incidence stays high. Anti-JCV antibody index and L-selectin (CD62L) have been proposed as additional risk stratification parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This study aimed at verifying and integrating both parameters into one algorithm for risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Multicentric, international cohorts of natalizumab-treated MS patients were assessed for JCV index (1921 control patients and nine pre-PML patients) and CD62L (1410 control patients and 17 pre-PML patients).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>CD62L values correlate with JCV serostatus, as well as JCV index values. Low CD62L in natalizumab-treated patients was confirmed and validated as a biomarker for PML risk with the risk factor \u201cCD62L low\u201d increasing a patient\u2019s relative risk 55-fold ( p &lt; 0.0001). Validation efforts established 86% sensitivity\/91% specificity for CD62L and 100% sensitivity\/59% specificity for JCV index as predictors of PML. Using both parameters identified 1.9% of natalizumab-treated patients in the reference center as the risk group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Both JCV index and CD62L have merit for risk stratification and share a potential biological relationship with implications for general PML etiology. A risk algorithm incorporating both biomarkers could strongly reduce PML incidence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1352458515607651","type":"journal-article","created":{"date-parts":[[2015,10,2]],"date-time":"2015-10-02T20:32:50Z","timestamp":1443817970000},"page":"1048-1060","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":55,"title":["PML risk stratification using anti-JCV antibody index and L-selectin"],"prefix":"10.1177","volume":"22","author":[{"given":"Nicholas","family":"Schwab","sequence":"first","affiliation":[{"name":"Department of Neurology, University of M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Schneider-Hohendorf","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Pignolet","sequence":"additional","affiliation":[{"name":"Pole des Neurosciences Centre Hospitalier Universitaire Toulouse, CPTP INSERM UMR 1043 et Universit\u00e9 de Toulouse, UPS, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Spadaro","sequence":"additional","affiliation":[{"name":"Clinical Neurobiology Unit, Regional Referring Multiple Sclerosis Centre (CRESM), Neuroscience Institute Cavalieri Ottolenghi (NICO), University Hospital San Luigi Gonzaga, Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"G\u00f6rlich","sequence":"additional","affiliation":[{"name":"Institute of Biostatistics and Clinical Research, University of M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Meinl","sequence":"additional","affiliation":[{"name":"Institute for Clinical Neuroimmunology, Ludwig-Maximilians-University Munich and Munich Cluster Systems Neurology (SyNergy), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Windhagen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinics Osnabr\u00fcck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Tackenberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Philipps University and University Clinics Gie\u00dfen and Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Breuer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Cant\u00f3","sequence":"additional","affiliation":[{"name":"Servei de Neurologia-Neuroimmunologia, Centre d\u2019Esclerosi M\u00faltiple de Catalunya (Cemcat), Institut de Recerca Vall d\u2019Hebron (VHIR), Hospital Universitari Vall d\u2019Hebron, Universitat Aut\u00f2noma de Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"K\u00fcmpfel","sequence":"additional","affiliation":[{"name":"Institute for Clinical Neuroimmunology, Ludwig-Maximilians-University Munich and Munich Cluster Systems Neurology (SyNergy), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Hohlfeld","sequence":"additional","affiliation":[{"name":"Institute for Clinical Neuroimmunology, Ludwig-Maximilians-University Munich and Munich Cluster Systems Neurology (SyNergy), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Siffrin","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Mainz, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Zipp","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ruhr University Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud A","family":"Du Pasquier","sequence":"additional","affiliation":[{"name":"Divisions of Immunology and Allergy and of Neurology, Centre Hospitalier Universitaire Vaudois, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kleinschnitz","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, 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