{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T08:56:10Z","timestamp":1777280170377,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T00:00:00Z","timestamp":1547510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS\u2010PI15\/00513"],"award-info":[{"award-number":["FIS\u2010PI15\/00513"]}],"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":["RD16\/0015\/0001"],"award-info":[{"award-number":["RD16\/0015\/0001"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Teriflunomide, a disease\u2010modifying treatment approved for multiple sclerosis (<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>), inhibits reversibly dihydroorotate dehydrogenase, an enzyme involved in de novo pyrimidine biosynthesis and down\u2010regulates proliferation of activated lymphocytes. We aimed to study the impact of this drug in the lymphocyte profiles of <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty\u2010five patients with relapsing\u2010remitting <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> who initiated teriflunomide treatment were included in the study. We studied peripheral blood mononuclear cells obtained before and 6 months after treatment initiation and explored effector, memory, and regulatory cells by flow cytometry. Wilcoxon matched pair tests were used to assess differences between basal and 6 months after treatment results. <jats:italic>P<\/jats:italic>\u2010values were corrected with Bonferroni test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>When explored T and B cell subsets, we observed a decrease in the percentages of terminally differentiated <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4+ T cells (<jats:italic>P<\/jats:italic> = 0.001) and plasmablasts (<jats:italic>P<\/jats:italic> &lt; 0.0001) after 6 months of treatment. These results were confirmed with the total cell number. When studied immunomodulatory cells, we observed a clear increase of monocytes expressing programmed death\u2010ligand 1 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1) (<jats:italic>P<\/jats:italic> = 0.005), which correlated negatively with all effector <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ T cell subsets. We also observed an increase in the percentage of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ T cells (<jats:italic>P<\/jats:italic> = 0.028) and monocytes (<jats:italic>P<\/jats:italic> = 0.04) producing <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Teriflunomide induces a specific reduction in effector T and B cells that have shown to play a role in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> course and an increase in immunomodulatory cells. Particularly, this drug induces the expression of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1, a molecule involved in tolerance to autoantigens, which can contribute to inhibit the abnormal immune response taking place in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.711","type":"journal-article","created":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T10:51:39Z","timestamp":1547549499000},"page":"355-363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Teriflunomide induces a tolerogenic bias in blood immune cells of MS patients"],"prefix":"10.1002","volume":"6","author":[{"given":"Silvia","family":"Medina","sequence":"first","affiliation":[{"name":"Department of Immunology Hospital Universitario Ram\u00f3n y Cajal IRYCIS Madrid Spain"},{"name":"The Spanish Network of Multiple Sclerosis (REEM) Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Sainz de la Maza","sequence":"additional","affiliation":[{"name":"The Spanish Network of Multiple Sclerosis (REEM) Spain"},{"name":"Department of Neurology Hospital Universitario Ram\u00f3n y Cajal IRYCIS Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia","family":"Villarrubia","sequence":"additional","affiliation":[{"name":"Department of Immunology Hospital Universitario Ram\u00f3n y Cajal IRYCIS Madrid Spain"},{"name":"The Spanish Network of Multiple Sclerosis (REEM) Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3132-1486","authenticated-orcid":false,"given":"Roberto","family":"\u00c1lvarez\u2010Lafuente","sequence":"additional","affiliation":[{"name":"The Spanish Network of Multiple Sclerosis (REEM) Spain"},{"name":"Department of Neurology Hospital Cl\u00ednico San Carlos IDISSC Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucienne","family":"Costa\u2010Frossard","sequence":"additional","affiliation":[{"name":"The Spanish Network of Multiple Sclerosis (REEM) Spain"},{"name":"Department of Neurology Hospital Universitario Ram\u00f3n y Cajal IRYCIS Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Arroyo","sequence":"additional","affiliation":[{"name":"The Spanish Network of Multiple Sclerosis (REEM) Spain"},{"name":"Department of Neurology Hospital Universitario Quir\u00f3nsalud Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enric","family":"Monreal","sequence":"additional","affiliation":[{"name":"The Spanish Network of Multiple Sclerosis (REEM) Spain"},{"name":"Department of Neurology Hospital Universitario Ram\u00f3n y Cajal IRYCIS Madrid 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