{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:03:46Z","timestamp":1780542226440,"version":"3.54.1"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["GR-2016-02364891"],"award-info":[{"award-number":["GR-2016-02364891"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Ministry of University and Research","award":["PRIN 2022"],"award-info":[{"award-number":["PRIN 2022"]}]},{"name":"Italian Ministry of University and Research","award":["ID 2022Y9LK8T"],"award-info":[{"award-number":["ID 2022Y9LK8T"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) exhibits substantial heterogeneity in inflammatory pathways and therapeutic response. The organic cation transporter OCTN1 (SLC22A4) and its rs1050152 missense variant (L503F) have been implicated in innate immune activation and disease susceptibility. We investigated whether OCTN1 variants modulate monocyte inflammatory responses and predict clinical outcomes in UC patients treated with anti-tumor necrosis factor \u03b1 (TNF\u03b1) agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We combined preclinical and clinical approaches. In THP-1 cells engineered for OCTN1 knockdown or variant-specific overexpression, and in primary monocytes isolated from genotyped donors and UC patients, we assessed by enzyme-linked immunosorbent assay and Western blot interleukin (IL)-1\u03b2 production following bacterial stimulation (peptidoglycan, Fusobacterium nucleatum, Escherichia coli, Salmonella). In the clinical study, UC patients initiating anti-TNF\u03b1 therapy were genotyped and evaluated for 1-year therapy persistence, steroid-free clinical remission, and endoscopic response. Logistic regression models were used to identify predictors of outcomes. An exploratory machine learning analysis (regularized logistic regression and neural networks) was performed to rank the variables contributing to each endpoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>OCTN1-deficient THP-1 cells showed markedly reduced interleukin-1\u03b2 secretion, whereas the same cell line or primary monocytes carrying the 503F variant exhibited significantly enhanced cytokine release upon microbial stimulation. On the clinical side, 105 patients with UC were enrolled. The homozygous 503F genotype (TT) was strongly associated with higher rates of steroid-free remission, endoscopic response, and therapy persistence. Heterozygous carriers displayed intermediate outcomes. Machine learning models demonstrated moderate predictive performance (area under the curve 0.60-0.72), consistently ranking OCTN1 among relevant, though not dominant, determinants of therapeutic success.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The OCTN1 503F variant enhances interleukin-1\u03b2\u2013mediated innate immune activation and is associated with improved long-term response to anti-TNF\u03b1 therapy in UC. These findings support OCTN1 genotyping as a promising component of future precision medicine strategies in inflammatory bowel disease and warrant confirmation in larger prospective multicenter cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ibd\/izag061","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:58:04Z","timestamp":1773838684000},"page":"1153-1162","source":"Crossref","is-referenced-by-count":0,"title":["OCTN1 variants shape innate immunity and predict individual response to anti-TNF\u03b1 in ulcerative colitis patients: An exploratory study"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0935-8853","authenticated-orcid":false,"given":"Pierluigi","family":"Puca","sequence":"first","affiliation":[{"name":"IBD Unit, Digestive Diseases Center (CEMAD), Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome,","place":["Italy"]},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore , Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Masi","sequence":"additional","affiliation":[{"name":"CEMAD Translational Research Laboratories, Digestive Disease Center, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS , Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Parello","sequence":"additional","affiliation":[{"name":"IBD Unit, Digestive Diseases Center (CEMAD), Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome,","place":["Italy"]},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore , Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Poscia","sequence":"additional","affiliation":[{"name":"UOC ISP Prevention and Surveillance of Infectious and Chronic Diseases, Department of Prevention, Local Health Authority (AST Ancona) , Jesi, 60035,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrada Mihaela","family":"Tudor","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Universit\u00e0 Cattolica del Sacro Cuore , Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Capobianco","sequence":"additional","affiliation":[{"name":"IBD Unit, Digestive Diseases Center (CEMAD), Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome,","place":["Italy"]},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore , Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Pane","sequence":"additional","affiliation":[{"name":"CEMAD Translational Research Laboratories, 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