{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T20:13:40Z","timestamp":1724357620875},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,7,22]],"date-time":"2017-07-22T00:00:00Z","timestamp":1500681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministry of Economy and Competitiveness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["MTM2015\u201064465\u2010C2\u20101\u2010R"],"award-info":[{"award-number":["MTM2015\u201064465\u2010C2\u20101\u2010R"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Government of Catalonia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007379","name":"ARSEP","doi-asserted-by":"publisher","award":["2016"],"award-info":[{"award-number":["2016"]}],"id":[{"id":"10.13039\/100007379","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify biomarkers associated with the development of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab (NTZ).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Relapsing\u2013remitting MS patients who developed PML under NTZ therapy (pre\u2010PML) and non\u2010PML NTZ\u2010treated patients (NTZ\u2010ctr) were included in the study. Cryopreserved peripheral blood mononuclear cells and serum samples collected at baseline, at 1\u2010 and 2\u2010year treated time points, and during PML were analyzed for gene expression by RNA sequencing and for serum protein levels by Luminex and enzyme\u2010linked immunosorbent assays, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among top differentially expressed genes in the RNA sequencing between pre\u2010PML and NTZ\u2010ctr patients, pathway analysis revealed a high representation of genes belonging to the following categories: proangiogenic factors (<jats:italic>MMP9<\/jats:italic>, <jats:italic>VEGFA<\/jats:italic>), chemokines (<jats:italic>CXCL1<\/jats:italic>, <jats:italic>CXCL5<\/jats:italic>, <jats:italic>IL8<\/jats:italic>, <jats:italic>CCL2<\/jats:italic>), cytokines (<jats:italic>IL1B<\/jats:italic>, <jats:italic>IFNG<\/jats:italic>), and plasminogen\u2010 and coagulation\u2010related molecules (<jats:italic>SERPINB2<\/jats:italic>, <jats:italic>PLAU<\/jats:italic>, <jats:italic>PLAUR<\/jats:italic>, <jats:italic>TFPI<\/jats:italic>, <jats:italic>THBD<\/jats:italic>). Serum protein levels for these candidates were measured in a 2\u2010step manner in a screening cohort and a validation cohort of pre\u2010PML and NTZ\u2010ctr patients. Only matrix metalloproteinase 9 (MMP9) was validated; in pre\u2010PML patients, MMP9 protein levels were significantly reduced at baseline compared with NTZ\u2010ctr patients, and levels remained lower at later time points during NTZ treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The results from this study suggest that the proangiogenic factor MMP9 may play a role as a biomarker associated with the development of PML in MS patients treated with NTZ. Ann Neurol 2017;82:186\u2013195.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24987","type":"journal-article","created":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T05:32:40Z","timestamp":1499319160000},"page":"186-195","source":"Crossref","is-referenced-by-count":15,"title":["Matrix metalloproteinase 9 is decreased in natalizumab\u2010treated multiple sclerosis patients at risk for progressive multifocal leukoencephalopathy"],"prefix":"10.1002","volume":"82","author":[{"given":"Nicolas","family":"Fissolo","sequence":"first","affiliation":[{"name":"Department of Neurology\u2013Neuroimmunology, Multiple Sclerosis Center of Catalonia, Vall d'Hebron Research Institute, Vall d'Hebron University Hospital Autonomous University of Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9atrice","family":"Pignolet","sequence":"additional","affiliation":[{"name":"Neurosciences Pole, Toulouse University Hospital Center, Physiopathology Center of Toulouse\u2013Purpan, National Institute of Health and Medical Research University of Toulouse, and Paul Sabatier University Toulouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Matute\u2010Blanch","sequence":"additional","affiliation":[{"name":"Department of Neurology\u2013Neuroimmunology, Multiple Sclerosis Center of Catalonia, Vall d'Hebron Research Institute, Vall d'Hebron University Hospital Autonomous University of Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Carlos","family":"Trivi\u00f1o","sequence":"additional","affiliation":[{"name":"Genomic Systems Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berta","family":"Mir\u00f3","sequence":"additional","affiliation":[{"name":"Statistics and Bioinformatics Unit Vall d'Hebron Research Institute Barcelona 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France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Vukusic","sequence":"additional","affiliation":[{"name":"Department of Neurology Lyon University Hospital Center Bron France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Papeix","sequence":"additional","affiliation":[{"name":"Department of Neurology Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Almoyna","sequence":"additional","affiliation":[{"name":"Chi Aix\u2010en\u2010Provence  Aix\u2010en\u2010Provence France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayman","family":"Tourbah","sequence":"additional","affiliation":[{"name":"Department of Neurology and Reims Faculty of Medicine, Reims University Hospital Center University of Reims Champagne\u2010Ardenne, Reims, and University of Paris VIII Saint\u2010Denis 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