{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T09:26:17Z","timestamp":1770283577467,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008359","name":"Maag Lever Darm Stichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intracellular methotrexate polyglutamates (MTX\u2010PGs) concentrations are measurable in red blood cells (RBCs) during MTX treatment. MTX\u2010PG<jats:sub>3<\/jats:sub> concentrations correlate with efficacy in patients with Crohn's disease (CD). Since RBCs are not involved in pathogenesis of CD and lack extended MTX metabolism, we determined MTX\u2010PGs accumulation in peripheral blood mononuclear cells (PBMCs: effector cells) and intestinal mucosa (target cells) and compared those with RBCs as a potential more precise biomarker.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a multicentre prospective cohort study, blood samples of patients with CD were collected during the first year of MTX therapy. Mucosal biopsies were obtained from non\u2010inflamed rectum and\/or inflamed intestine. MTX\u2010PGs concentrations in mucosa, PBMCs and RBCs were measured by liquid chromatography\u2013tandem mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From 80 patients with CD, a total of 27 mucosal biopsies, 9 PBMC and 212 RBC samples were collected. From 12\u2009weeks of MTX therapy onwards, MTX\u2010PG<jats:sub>3<\/jats:sub> was the most predominant species (33%) in RBCs. In PBMCs, the distribution was skewed towards MTX\u2010PG<jats:sub>1<\/jats:sub> (48%), which accounted for an 18 times higher concentration than in RBCs. Long\u2010chain MTX\u2010PGs were highly present in mucosa: 21% of MTX\u2010PG<jats:sub>total<\/jats:sub> was MTX\u2010PG<jats:sub>5<\/jats:sub>. MTX\u2010PG<jats:sub>6<\/jats:sub> was measurable in all biopsies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MTX\u2010PG patterns differ between mucosa, PBMCs and RBCs of patients with CD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcpt.14047","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T09:26:55Z","timestamp":1720430815000},"page":"308-320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Methotrexate accumulation in target intestinal mucosa and white blood cells differs from non\u2010target red blood cells of patients with Crohn's disease"],"prefix":"10.1111","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2415-5114","authenticated-orcid":false,"given":"Maartje M.","family":"van de Meeberg","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute Amsterdam University Medical Centre VU University Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Gastroenterology and Hepatology University Medical Centre Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janani","family":"Sundaresan","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Amsterdam UMC  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marry","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Amsterdam UMC  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerrit","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Amsterdam University Medical Centre VU University Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard A.","family":"Struys","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Amsterdam UMC  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herma H.","family":"Fidder","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Medical Centre Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bas","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Medical Centre Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wout G. 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