Z Gastroenterol 2025; 63(08): e367
DOI: 10.1055/s-0045-1810635
Abstracts | DGVS/DGAV
Freie Vorträge

Transcriptional profiling of crohn’s disease behavioral phenotypes reveals distinct fibrosis-associated signatures

Authors

  • M Lehmann

    1   Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Deutschland

  • C Plattner

    2   Institute of Bioinformatics, Medical University of Innsbruck, Biocenter, Innsbruck, Österreich

  • H H Gluschke

    1   Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Deutschland

  • A Huck

    1   Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Deutschland

  • L-M Haag

    1   Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Deutschland

  • Z Trajanoski

    2   Institute of Bioinformatics, Medical University of Innsbruck, Biocenter, Innsbruck, Österreich
    3   The Transregio 241 IBDome Consortium, Berlin, Deutschland

  • A A Kühl

    4   Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, iPATH.Berlin, Berlin, Deutschland
    3   The Transregio 241 IBDome Consortium, Berlin, Deutschland

  • B Siegmund

    1   Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Medical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Deutschland
    3   The Transregio 241 IBDome Consortium, Berlin, Deutschland
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Introduction: Crohn’s disease (CD) presents with different behavioral phenotypes: non-stricturing/non-penetrating (B1), stricturing (B2), and stricturing/penetrating (B3). Whether these phenotypes are purely clinical or underpinned by distinct molecular mechanisms remains unclear.

Objectives: This study aimed to identify transcriptional differences between CD behavioral phenotypes and to uncover potential phenotype-specific pathogenic programs.

Methods: Bulk RNA sequencing was performed on 239 intestinal biopsies (170 CD, 69 healthy controls) of the IBDome cohort. Differential expression analysis, gene ontology (GO) annotation, and STRING network analysis were conducted to explore the impact of inflammation, tissue origin, and clinical phenotype on gene expression.

Results: Tissue origin and inflammation emerged as primary drivers of transcriptional variation. B2 biopsies showed significant upregulation of fibrosis-associated genes (e.g., EGR1, CCN1, CCN2, HBEGF), indicating a persistent profibrotic transcriptional program, even in non-inflamed tissue. In contrast, B3 biopsies exhibited a heterogeneous pattern of immune activation without a distinct fibrotic network. Direct comparisons revealed a clear molecular distinction between B2 and B1 but only subtle differences between B2 and B3.

Conclusion: Stricturing CD (B2) represents a distinct molecular entity characterized by a sustained profibrotic program independent of active inflammation. The stricturing/penetrating phenotype (B3) appears more heterogeneous at the molecular level.

Abstracts

Präsentiert in der Sitzung: CED: Wegkreuzungen in der Therapie

Donnerstag, 18. September 2025, 11:30 – 13:00, Saal 1



Publikationsverlauf

Artikel online veröffentlicht:
04. September 2025

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