{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:59:52Z","timestamp":1784735992023,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T00:00:00Z","timestamp":1492387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytometry Part B Clinical"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>In natalizumab\u2010treated relapsing\u2010remitting MS (RRMS) patients, various extended interval dosing strategies are under evaluation to minimize severe treatment\u2010associated side effects, mainly progressive multifocal leukoencephalopathy development. Up to now, it has not been presented any approach, even in form of assay design, to determine the optimal percentage of CD49d receptor occupancy (RO) associated with a favorable clinical, radiological, and immunological response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A multiparametric quantitative flow cytometry method was settled to measure CD49d RO on peripheral blood lymphocytes. The analytical protocol was tested in a 6\u2010month follow\u2010up from 19 RRMS patients treated with the natalizumab standard dosing of every 4 weeks or an extended\u2010interval dosing of every 6 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Extended natalizumab dose schedule promoted an increase of CD49d molecules per cell surface and a reduction of CD49d RO levels. The reduction observed on CD49d RO was not only depending on dose schedule but also on individual parameters such as body mass. Interestingly, individual clinical outcome was apparently the same between the different dose schedules or even better with the extended interval dosing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Following up CD49d RO levels with a well\u2010regulated monitoring work scheme is crucial to further identify over\u2010\/under\u2010treated patients and to define a safe, personalized natalizumab regimen. \u00a9 2017 International Clinical Cytometry Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/cyto.b.21527","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T20:04:06Z","timestamp":1491422646000},"page":"327-333","source":"Crossref","is-referenced-by-count":20,"title":["Monitoring CD49d Receptor Occupancy: A Method to Optimize and Personalize Natalizumab Therapy in Multiple Sclerosis Patients"],"prefix":"10.1002","volume":"94","author":[{"given":"Joan","family":"Pu\u00f1et\u2010Ortiz","sequence":"first","affiliation":[{"name":"Division of Immunology Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti Badalona Spain"},{"name":"Department of Cellular Biology Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Vicente","family":"Herv\u00e1s\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Multiple Sclerosis Unit, University Hospital Germans Trias i Pujol Badalona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aina","family":"Teniente\u2010Serra","sequence":"additional","affiliation":[{"name":"Division of Immunology Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti Badalona Spain"},{"name":"Department of Cellular Biology Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cano\u2010Orgaz","sequence":"additional","affiliation":[{"name":"Neurology Service Consorci Sanitari del Maresme Matar\u00f3 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e9","family":"Mansilla","sequence":"additional","affiliation":[{"name":"Division of Immunology Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti Badalona Spain"},{"name":"Department of Cellular Biology Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibiana","family":"Quirant\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Division of Immunology Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti Badalona Spain"},{"name":"Department of Cellular Biology Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Navarro\u2010Barriuso","sequence":"additional","affiliation":[{"name":"Division of Immunology Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti Badalona Spain"},{"name":"Department of Cellular Biology Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Fern\u00e1ndez\u2010Sanmart\u00edn","sequence":"additional","affiliation":[{"name":"Flow Cytometry Facility Germans Trias i Pujol Research Institute, Campus Can Ruti Badalona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Presas\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Multiple Sclerosis Unit, University Hospital Germans Trias i Pujol Badalona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ramo\u2010Tello","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Multiple Sclerosis Unit, University Hospital Germans Trias i Pujol Badalona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Mar\u00eda","family":"Mart\u00ednez\u2010C\u00e1ceres","sequence":"additional","affiliation":[{"name":"Division of Immunology Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti Badalona Spain"},{"name":"Department of Cellular Biology Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona 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