{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:03:19Z","timestamp":1773810199040,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization \u201cblind spot\u201d was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients\u2019 humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF.<\/jats:p>","DOI":"10.3390\/v12121380","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T20:25:49Z","timestamp":1606940749000},"page":"1380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors"],"prefix":"10.3390","volume":"12","author":[{"given":"Morgane","family":"Solis","sequence":"first","affiliation":[{"name":"Virology Laboratory, Strasbourg University Hospitals, 67000 Strasbourg, France"},{"name":"INSERM UMR-S 1109 LabEx TRANSPLANTEX, Strasbourg University, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lien","family":"Guffroy","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases, Strasbourg University Hospitals, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6018-4057","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Lersy","sequence":"additional","affiliation":[{"name":"Service d\u2019Imagerie 2, Strasbourg University Hospitals, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Soulier","sequence":"additional","affiliation":[{"name":"INSERM UMR-S 1109 LabEx TRANSPLANTEX, Strasbourg University, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floriane","family":"Gallais","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Strasbourg University Hospitals, 67000 Strasbourg, France"},{"name":"INSERM UMR-S 1109 LabEx TRANSPLANTEX, Strasbourg University, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0061-9378","authenticated-orcid":false,"given":"Mathilde","family":"Renaud","sequence":"additional","affiliation":[{"name":"Neurology Department, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg (FMTS), Strasbourg University Hospitals, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3497-4669","authenticated-orcid":false,"given":"Nawal","family":"Douiri","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Strasbourg University Hospitals, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7767-5362","authenticated-orcid":false,"given":"Xavier","family":"Argemi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Strasbourg University Hospitals, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yves","family":"Hansmann","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Strasbourg University Hospitals, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00f4me","family":"De S\u00e8ze","sequence":"additional","affiliation":[{"name":"Neurology Department, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg (FMTS), Strasbourg University Hospitals, 67000 Strasbourg, France"},{"name":"Clinical Investigation Center, INSERM 1434, Strasbourg University Hospitals, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane","family":"Kremer","sequence":"additional","affiliation":[{"name":"Service d\u2019Imagerie 2, Strasbourg University Hospitals, 67000 Strasbourg, France"},{"name":"Engineering Science, Computer Science and Imaging Laboratory (ICube), Integrative Multimodal Imaging in Healthcare, UMR 7357, University of Strasbourg-CNRS, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samira","family":"Fafi-Kremer","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Strasbourg University Hospitals, 67000 Strasbourg, France"},{"name":"INSERM UMR-S 1109 LabEx TRANSPLANTEX, Strasbourg University, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1080\/1040841X.2016.1189873","article-title":"45 years after the discovery of human polyomaviruses BK and JC: Time to speed up the understanding of associated diseases and treatment approaches","volume":"43","author":"Barth","year":"2017","journal-title":"Crit. 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Neurol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/12\/1380\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:40:42Z","timestamp":1760179242000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/12\/1380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,2]]},"references-count":29,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["v12121380"],"URL":"https:\/\/doi.org\/10.3390\/v12121380","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,2]]}}}