Evidence map›Paper›PMID 42378710›Full record

ArticleJournal of Crohn's & colitis2026

Impaired keratinization activity in perianal Crohn's fistulas is associated with poor prognosis.

Marte A J Becker, Pim J Koelink, Sarah Ouahoud, Sander M Meisner, Vanesa Muncan, Gerald Nabozny, Frank Li, Job Saris, Willem A Bemelman, Geert R D'Haens and 2 more

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Article in Journal of Crohn's & colitis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Marte A J BeckerDepartment of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-7881-4958
Pim J KoelinkTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Sarah OuahoudTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Sander M MeisnerTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Vanesa MuncanDepartment of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Gerald NaboznyDepartment of Immunology and Respiratory Diseases Research, Research and Development Boehringer-Ingelheim, Ridgefield, CT, United States.
Frank LiDepartment of Global Computational Biology and Data Sciences, Research and Development Boehringer-Ingelheim, Ridgefield, CT, United States.
Job SarisDepartment of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Willem A BemelmanDepartment of Surgery, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Geert R D'HaensDepartment of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Christianne J BuskensDepartment of Surgery, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0001-9425-8683
Manon E WildenbergDepartment of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Funding

Boehringer-Ingelheim
6 · The paper itself

Abstract

backgroundPerianal fistulas remain a major complication in Crohn's disease, profoundly impacting quality of life. Although often therapy refractory, strong heterogeneity exists between patients, both in clinical behavior and therapy response. In this study, we aimed to identify biological factors involved in the clinical behavior of perianal fistulas, allowing better stratification.

methodsForty-nine patients were included (Crohn's n = 36, cryptoglandular n = 13). Gene expression was analyzed in internal fistula openings and tracts by RNA sequencing. Data were verified using spatial transcriptomics and functionally in human adult organoid cultures. A gene-module score for keratinization activity was calculated and correlated to the Crohn's TOpClass classification as well as to long-term fistula outcomes.

resultsPerianal fistulas were associated with the development of stratified squamous epithelium, expressing specific keratins (KRT5, KRT7, and KRT13). In human organoid models, exposing intestinal mucosa to a pro-inflammatory cytokine mixture partially induced similar changes, supporting rectal mucosal redifferentiation in response to perianal wounding. A gene-module score based on the keratinization-associated markers showed a decreasing gradient from cryptoglandular to mild Crohn-related to severe Crohn-related fistula (0.448 vs. -0.125 vs. -0.448, P = .018). Interestingly, the score was also predictive of long-term outcomes: Patients with low keratinization often showed progressive disease (14/20 patients), whereas this was not seen in the high keratinization group (0/16, P < .001).

conclusionWe identify an epithelial redifferentiation process characterized by a keratinization-associated gene module as part of the healing process in perianal fistula. The extent of the keratinization not only distinguished Crohn-related from cryptoglandular fistulas but also aligned with disease severity and healing potential.

Indexed as

Crohn DiseaseKeratinsRectal FistulaAdultFemaleHumansIntestinal MucosaMaleMiddle AgedPrognosisKeratinsinflammatory bowel diseaseperianal fistulawound healing

Identifiers

PMID42378710
PMCPMC13318234

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.