P084 Ileal gene expression changes are associated with colonic disease activity in patients with ulcerative colitis
Notice bibliographique
Résumé
ulcerative colitis (UC) is a chronic, relapsing disorder characterised by inflammation limited to the colon and rectum. From a pathophysiologic point of view, there is no explanation for the spatial restriction of inflammation, and studies on the involvement of ileal changes in patients with UC are scarce. Here we therefore aimed to investigate gene expression profiles of the unaffected ileum of UC patients, and compare these to non-IBD controls to see whether these factors contribute to disease perpetuation. Biopsies were collected from normal terminal ileum of 16 patients with UC (50% male, median [interquartile range, IQR] age 49.5 [29.4–66.7] years, median [IQR] disease duration 11 [7–15.5] years, Montreal disease extent 1 E1/8 E2/7 E3); and 14 controls (42.9% male, age 56.7 [45.7–60.6] years) who underwent endoscopy for polyp screening. Patients with backwash ileitis were excluded. Disease activity for UC was based on endoscopic findings, with active disease defined as Mayo endoscopic subscore ≥2. Next-generation single-end sequencing was performed using the Illumina HiSeq 4000 NGS platform. One sample was removed from analysis due to suboptimal read counts. Differential expression analysis was performed using DESeq. One-fourth of UC patients had active colonic disease at the time the biopsy was taken. Comparative analyses of gene expression levels between active UC patients and controls identified seven genes with significant different expression (false discovery rate (FDR) ≤0.1 and fold change (FC) ≥2). The top signals were seen for MUC4 which was significantly upregulated (FC=3.89, FDR = 0.01), and FAM21B which was significantly downregulated (FC = 0.06, FDR = 0.05) in ileum of active UC compared with controls. All other significant genes were upregulated (CEACAM20, CASP10, LRG1, PDZK1IP1, and GRAMD2). Pathway analysis showed association with antiviral innate immunity and apoptosis signalling. When comparing ileal samples from inactive UC patients with controls, however, we did not observe any differentially expressed genes after adjustment for multiple testing. Also among UC patients, no differentially expressed genes were seen for those with active colonic disease vs. those without. Our study showed that—while no overt inflammation is generally seen in ileum of UC patients—subtle ileal gene expression changes do occur in patients depending on disease activity of the colon. The identified genes are involved in a range of UC-associated biological processes, including barrier function, cell trafficking, apoptosis, angiogenesis, and immune signalling. Whether ileal changes in these processes should be seen as a driving factor in UC or secondary epiphenomenon remains to be confirmed with functional studies.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».