{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T08:56:14Z","timestamp":1777280174637,"version":"3.51.4"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/02099"],"award-info":[{"award-number":["PI15\/02099"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01766"],"award-info":[{"award-number":["PI18\/01766"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FI19\/00149"],"award-info":[{"award-number":["FI19\/00149"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Regional Development Fund","award":["PI15\/02099"],"award-info":[{"award-number":["PI15\/02099"]}]},{"name":"European Regional Development Fund","award":["PI18\/01766"],"award-info":[{"award-number":["PI18\/01766"]}]},{"name":"European Regional Development Fund","award":["FI19\/00149"],"award-info":[{"award-number":["FI19\/00149"]}]},{"name":"European Social Fund","award":["PI15\/02099"],"award-info":[{"award-number":["PI15\/02099"]}]},{"name":"European Social Fund","award":["PI18\/01766"],"award-info":[{"award-number":["PI18\/01766"]}]},{"name":"European Social Fund","award":["FI19\/00149"],"award-info":[{"award-number":["FI19\/00149"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fingolimod is an immunomodulatory sphingosine-1-phosphate (S1P) analogue approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The identification of biomarkers of clinical responses to fingolimod is a major necessity in MS to identify optimal responders and avoid the risk of disease progression in non-responders. With this aim, we used RNA sequencing to study the transcriptomic changes induced by fingolimod in peripheral blood mononuclear cells of MS-treated patients and their association with clinical response. Samples were obtained from 10 RRMS patients (five responders and five non-responders) at baseline and at 12 months of fingolimod therapy. Fingolimod exerted a vast impact at the transcriptional level, identifying 7155 differentially expressed genes (DEGs) compared to baseline that affected the regulation of numerous signaling pathways. These DEGs were predominantly immune related, including genes associated with S1P metabolism, cytokines, lymphocyte trafficking, master transcription factors of lymphocyte functions and the NF-kB pathway. Responder and non-responder patients exhibited a differential transcriptomic regulation during treatment, with responders presenting a higher number of DEGs (6405) compared to non-responders (2653). The S1P, NF-kB and TCR signaling pathways were differentially modulated in responder and non-responder patients. These transcriptomic differences offer the potential of being exploited as biomarkers of a clinical response to fingolimod.<\/jats:p>","DOI":"10.3390\/ijms25031372","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T04:17:40Z","timestamp":1705983460000},"page":"1372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Response to Fingolimod in Multiple Sclerosis Patients Is Associated with a Differential Transcriptomic Regulation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1155-081X","authenticated-orcid":false,"given":"Alicia","family":"S\u00e1nchez-Sanz","sequence":"first","affiliation":[{"name":"Neuroimmunology Unit, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Mu\u00f1oz-Viana","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5745-7544","authenticated-orcid":false,"given":"Julia","family":"Sab\u00edn-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Moreno-Torres","sequence":"additional","affiliation":[{"name":"Demyelinating Diseases Unit, Hospital Universitario Fundaci\u00f3n Jim\u00e9nez D\u00edaz, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Brea-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Radiodiagnostic Division, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ofir","family":"Rodr\u00edguez-De la Fuente","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Garc\u00eda-Merino","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain"},{"name":"Department of Neurology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain"},{"name":"Department of Medicine, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Red Espa\u00f1ola de Esclerosis M\u00faltiple (REEM), 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7168-6175","authenticated-orcid":false,"given":"Antonio J.","family":"S\u00e1nchez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain"},{"name":"Red Espa\u00f1ola de Esclerosis M\u00faltiple (REEM), 08028 Barcelona, Spain"},{"name":"Biobank, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nri3871","article-title":"Immunopathology of multiple sclerosis","volume":"15","author":"Dendrou","year":"2015","journal-title":"Nat. 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