Therapeutic targets established in adult ulcerative colitis exhibit correlations with disease severity and pathological relevance in pediatric pouchitis

Therapeutic targets established in adult ulcerative colitis exhibit correlations with disease severity and pathological relevance in pediatric pouchitis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Therapeutic targets established in adult ulcerative colitis exhibit correlations with disease severity and pathological relevance in pediatric pouchitis Sayaka Otake, Enkhtuvshin Khorolgarav, Takehiko Yokobori, Navchaa Gombodorj, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7941387/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted 11 You are reading this latest preprint version Abstract Pediatric pouchitis has no established treatment strategy, and management is particularly challenging in recurrent or antibiotic-refractory cases. Tumor necrosis factor alpha (TNF-α) and mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) are established and emerging therapeutic targets, respectively, in adult ulcerative colitis (UC) and pouchitis; however, their expression profiles and clinical relevance in pediatric pouchitis remain unclear. Therefore, we evaluated the pathological and clinical significance of TNF-α and MAdCAM-1 in pediatric patients with pouchitis. We performed immunohistochemical analysis of surgically resected ileal tissues and subsequent pouch biopsy specimens obtained from 10 pediatric patients with UC. Paired pouchitis biopsies were collected during both active (high pouchitis disease activity index, PDAI) and improved (low PDAI) phases. TNF-α, MAdCAM-1, and immune cell markers (CD68, CD163, and CD8) in the mucosal stroma were quantitatively assessed using HALO image analysis. Compared with baseline ileal tissues, pouchitis specimens showed increased MAdCAM-1-positive vasculature and infiltration of CD68- and CD163-positive cells. In paired specimens, MAdCAM-1, TNF-α, and CD68 expression was significantly reduced in low-PDAI tissues. MAdCAM-1 and TNF-α expression was positively correlated with inflammatory cell infiltration. As the first demonstration of MAdCAM-1 and TNF-α upregulation in pediatric pouchitis and their association with disease severity, this study highlights the pathological relevance of adult UC therapeutic targets for pediatric pouchitis. Biological sciences/Cancer Health sciences/Diseases Health sciences/Gastroenterology Biological sciences/Immunology Health sciences/Medical research pediatric pouchitis ulcerative colitis immunohistochemistry macrophages disease severity Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 17 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 31 Dec, 2025 Reviews received at journal 28 Dec, 2025 Reviews received at journal 23 Dec, 2025 Reviewers agreed at journal 20 Dec, 2025 Reviews received at journal 11 Dec, 2025 Reviewers agreed at journal 08 Dec, 2025 Reviewers agreed at journal 08 Dec, 2025 Reviewers invited by journal 08 Dec, 2025 Editor assigned by journal 20 Nov, 2025 Submission checks completed at journal 14 Nov, 2025 First submitted to journal 14 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7941387","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":557316064,"identity":"63ac5088-6dc2-4449-9d83-942888f90a06","order_by":0,"name":"Sayaka Otake","email":"","orcid":"","institution":"Gunma University","correspondingAuthor":false,"prefix":"","firstName":"Sayaka","middleName":"","lastName":"Otake","suffix":""},{"id":557316065,"identity":"91714fd0-910b-4845-a4e2-68cc628ef3f2","order_by":1,"name":"Enkhtuvshin Khorolgarav","email":"","orcid":"","institution":"Gunma 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pouchitis","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"pediatric pouchitis, ulcerative colitis, immunohistochemistry, macrophages, disease severity","lastPublishedDoi":"10.21203/rs.3.rs-7941387/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7941387/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Pediatric pouchitis has no established treatment strategy, and management is particularly challenging in recurrent or antibiotic-refractory cases. Tumor necrosis factor alpha (TNF-α) and mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) are established and emerging therapeutic targets, respectively, in adult ulcerative colitis (UC) and pouchitis; however, their expression profiles and clinical relevance in pediatric pouchitis remain unclear. Therefore, we evaluated the pathological and clinical significance of TNF-α and MAdCAM-1 in pediatric patients with pouchitis. We performed immunohistochemical analysis of surgically resected ileal tissues and subsequent pouch biopsy specimens obtained from 10 pediatric patients with UC. Paired pouchitis biopsies were collected during both active (high pouchitis disease activity index, PDAI) and improved (low PDAI) phases. TNF-α, MAdCAM-1, and immune cell markers (CD68, CD163, and CD8) in the mucosal stroma were quantitatively assessed using HALO image analysis. Compared with baseline ileal tissues, pouchitis specimens showed increased MAdCAM-1-positive vasculature and infiltration of CD68- and CD163-positive cells. In paired specimens, MAdCAM-1, TNF-α, and CD68 expression was significantly reduced in low-PDAI tissues. MAdCAM-1 and TNF-α expression was positively correlated with inflammatory cell infiltration. As the first demonstration of MAdCAM-1 and TNF-α upregulation in pediatric pouchitis and their association with disease severity, this study highlights the pathological relevance of adult UC therapeutic targets for pediatric pouchitis.","manuscriptTitle":"Therapeutic targets established in adult ulcerative colitis exhibit correlations with disease severity and pathological relevance in pediatric pouchitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-10 03:48:37","doi":"10.21203/rs.3.rs-7941387/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-31T05:49:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-28T14:54:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-23T22:00:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"162608903740034283370853888461050494232","date":"2025-12-21T00:35:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-11T16:25:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"337306532055344301626392172933983954971","date":"2025-12-09T02:39:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"335663641380317757296447281633264794573","date":"2025-12-08T13:19:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-08T11:45:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-20T15:11:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-15T04:11:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-11-15T04:07:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b5e3d32e-ff9b-41f3-a068-aa1931a84537","owner":[],"postedDate":"December 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":59313530,"name":"Biological sciences/Cancer"},{"id":59313531,"name":"Health sciences/Diseases"},{"id":59313532,"name":"Health sciences/Gastroenterology"},{"id":59313533,"name":"Biological sciences/Immunology"},{"id":59313534,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-02-23T16:00:55+00:00","versionOfRecord":{"articleIdentity":"rs-7941387","link":"https://doi.org/10.1038/s41598-026-40173-7","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-02-17 15:57:13","publishedOnDateReadable":"February 17th, 2026"},"versionCreatedAt":"2025-12-10 03:48:37","video":"","vorDoi":"10.1038/s41598-026-40173-7","vorDoiUrl":"https://doi.org/10.1038/s41598-026-40173-7","workflowStages":[]},"version":"v1","identity":"rs-7941387","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7941387","identity":"rs-7941387","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}