{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T13:43:18Z","timestamp":1776001398728,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,1,30]],"date-time":"2015-01-30T00:00:00Z","timestamp":1422576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness","award":["PI12-00239, SAF 2012-34670, RD12\/0032\/0005"],"award-info":[{"award-number":["PI12-00239, SAF 2012-34670, RD12\/0032\/0005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"Objective<\/jats:title>Progressive multifocal leukoencephalopathy (PML) is a serious side effect associated with natalizumab treatment in multiple sclerosis (MS). PML risk increases in individuals seropositive for anti\u2013John Cunningham virus (JC) antibodies, with prolonged duration of natalizumab treatment, and with prior exposure to immunosuppressants. We explored whether the presence of lipid\u2010specific immunoglobulin M oligoclonal bands in cerebrospinal fluid (CSF; IgM bands), a recognized marker of highly inflammatory MS, may identify individuals better able to counteract the potential immunosuppressive effect of natalizumab and hence be associated with a reduced risk of developing PML.<\/jats:p><\/jats:sec>Methods<\/jats:title>We studied 24 MS patients who developed PML and another 343 who did not suffer this opportunistic infection during natalizumab treatment. Patients were recruited at 25 university hospitals. IgM bands were studied by isoelectric focusing and immunodetection. CSF lymphocyte counts were explored in 151 MS patients recruited at Ramon y Cajal Hospital in Madrid, Spain.<\/jats:p><\/jats:sec>Results<\/jats:title>IgM bands were independently associated with decreased PML risk (odds ratio [OR]\u2009=\u200945.9, 95% confidence interval [CI]\u2009=\u20095.9\u2013339.3, p<\/jats:italic>\u2009<\u20090.0001) in patients treated with natalizumab. They were also associated with significantly higher CSF CD4, CD8, and B\u2010cell numbers. Patients positive for IgM bands and anti\u2010JC antibodies had similar levels of reduced PML risk to those who were anti\u2010JC negative (OR\u2009=\u20091.55, 95% CI\u2009=\u20090.09\u201325.2, p<\/jats:italic>\u2009=\u20091.0). Higher risk was observed in patients positive for anti\u2010JC antibodies and negative for IgM bands (19% of the total cohort, OR\u2009=\u200959.71, 95% CI\u2009=\u200913.6\u2013262.2).<\/jats:p><\/jats:sec>Interpretation<\/jats:title>The presence of IgM bands reflects a process that may diminish the risk of PML by counteracting the excess of immunosuppression that may occur during natalizumab therapy. Ann Neurol 2015;77:447\u2013457<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24345","type":"journal-article","created":{"date-parts":[[2015,1,7]],"date-time":"2015-01-07T22:02:22Z","timestamp":1420668142000},"page":"447-457","source":"Crossref","is-referenced-by-count":45,"title":["Lipid\u2010specific immunoglobulin M<\/scp> bands in cerebrospinal fluid are associated with a reduced risk of developing progressive multifocal leukoencephalopathy during treatment with natalizumab"],"prefix":"10.1002","volume":"77","author":[{"given":"Luisa M.","family":"Villar","sequence":"first","affiliation":[{"name":"Department of Immunology Ram\u00f3n y Cajal University Hospital, Institute Ramon y Cajal for Biomedical Research Madrid Spain"},{"name":"Spanish Network for the Research in Multiple Sclerosis Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucienne","family":"Costa\u2010Frossard","sequence":"additional","affiliation":[{"name":"Spanish Network for the Research in Multiple Sclerosis Spain"},{"name":"Department of Neurology Ramon y Cajal University Hospital Institute Ramon y Cajal for Biomedical Research Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Masterman","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institute Karolinska University Hospital Huddinge Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Spanish Network for the Research in Multiple Sclerosis Spain"},{"name":"Department of Neurology Regional University Hospital of Malaga Malaga Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Montalban","sequence":"additional","affiliation":[{"name":"Spanish Network for the Research in Multiple Sclerosis Spain"},{"name":"Department of Neurology\u2010Neuroimmunology Catalunya Center for Multiple Sclerosis Vall d'Hebron Institute of Research Vall d'Hebron University Hospital Autonomous University of Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bonaventura","family":"Casanova","sequence":"additional","affiliation":[{"name":"Spanish Network for the Research in Multiple Sclerosis Spain"},{"name":"Department of Neurology La Fe University Hospital Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Spanish Network for the Research in Multiple Sclerosis Spain"},{"name":"Department of Neurology Virgen Macarena University Hospital Seville Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Coret","sequence":"additional","affiliation":[{"name":"Spanish Network for the Research in Multiple Sclerosis Spain"},{"name":"Department of Neurology Clinic University Hospital of Valencia Valencia 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