{"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":1789674546989,"version":"4.0.1"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,10,25]],"date-time":"2015-10-25T00:00:00Z","timestamp":1445731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008061","name":"Fundaci\u00f3n Mutua Madrile\u00f1a","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008061","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":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Progressive multifocal leukoencephalopathy (<jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>) cases have arisen amongst multiple sclerosis patients treated with natalizumab. Our objective was to gain a better understanding of the mechanisms that underlie the John Cunningham virus (<jats:styled-content style=\"fixed-case\">JCV<\/jats:styled-content>) infection which causes <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A study was made of (i) the quarterly <jats:styled-content style=\"fixed-case\">JCV DNA<\/jats:styled-content> levels in peripheral blood mononuclear cells (<jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>s), serum and urine samples in 100 multiple sclerosis patients during their natalizumab treatment (3\u201339 months), (ii) the association between human leukocyte antigen (<jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>) class <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> and the previous viral detection and (iii) the identification of the <jats:styled-content style=\"fixed-case\">JCV<\/jats:styled-content> variants in those patients suspected of having <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(i) <jats:styled-content style=\"fixed-case\">JCV DNA<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>s and\/or serum was detected in 23% of our cohort. Patients with an intermittent <jats:styled-content style=\"fixed-case\">JCV<\/jats:styled-content> excretion in urine had a significant increase of the viral load and prevalence in this compartment during natalizumab treatment. (ii) The frequency of the <jats:italic><jats:styled-content style=\"fixed-case\">DRB<\/jats:styled-content>1*07\/<jats:styled-content style=\"fixed-case\">DQA<\/jats:styled-content>1*02:01\/<jats:styled-content style=\"fixed-case\">DQB<\/jats:styled-content>1*02:02<\/jats:italic> haplotype tended to be higher in patients with detectable versus undetectable <jats:styled-content style=\"fixed-case\">JCV DNA<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>s (<jats:italic>P<\/jats:italic><jats:sub>corrected<\/jats:sub> = 0.108). (iii) The variants in <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>s and serum of the non\u2010<jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> patient matched the archetype. In the patient with non\u2010fatal <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>, the archetype and the same neurotropic variant in <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>s, serum and cerebrospinal fluid was identified at the time <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> was diagnosed, whereas in the patient with a worse <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> prognosis, four neurotropic variants in the three previous compartments were found by the <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The detection of the neurotropic variant in blood during natalizumab treatment could be critical in the prevention of the development of severe <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>, since this variant appears simultaneously with the clinical symptoms of <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> and mutates quickly.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.12834","type":"journal-article","created":{"date-parts":[[2015,10,26]],"date-time":"2015-10-26T03:59:39Z","timestamp":1445831979000},"page":"182-189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Monitoring the John Cunningham virus throughout natalizumab treatment in multiple sclerosis patients"],"prefix":"10.1111","volume":"23","author":[{"given":"M. I.","family":"Dom\u00ednguez\u2010Mozo","sequence":"first","affiliation":[{"name":"Department of Neurology Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC) Hospital Cl\u00ednico San Carlos Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Garc\u00eda\u2010Montojo","sequence":"additional","affiliation":[{"name":"Department of Neurology Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC) Hospital Cl\u00ednico San Carlos Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Arias\u2010Leal","sequence":"additional","affiliation":[{"name":"Department of Neurology Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC) Hospital Cl\u00ednico San Carlos Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1.","family":"Garc\u00eda\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Neurology Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC) Hospital Cl\u00ednico San Carlos Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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