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- Title
Gut Barrier Dysfunction—A Primary Defect in Twins with Crohn's Disease Predominantly Caused by Genetic Predisposition.
- Authors
Keita, Åsa V; Lindqvist, Carl Mårten; Öst, Åke; Magana, Carlos D L; Schoultz, Ida; Halfvarson, Jonas
- Abstract
Background and Aims The aetiology of Crohn's disease is poorly understood. By investigating twin pairs discordant for Crohn's disease, we aimed to assess whether the dysregulated barrier represents a cause or a consequence of inflammation and to evaluate the impact of genetic predisposition on barrier function. Methods Ileal biopsies from 15 twin pairs discordant for Crohn's disease [monozygotic n = 9, dizygotic n = 6] and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to51Chromium [Cr]-EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid. Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins. Results Healthy co-twins and affected twins displayed increased51Cr-EDTA permeability at 120 min, both with acetylsalicylic acid [ p < 0.001] and without [ p < 0.001] when compared with controls. A significant increase in51Cr-EDTA flux was already seen at 20 min in healthy monozygotic co-twins compared with controls [ p ≤0.05] when stratified by zygosity, but not in healthy dizygotic co-twins. No difference in E. coli passage was observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins [ p < 0.05] and affected twins [ p < 0.05] compared with external controls, while ELISA only showed lower tricellulin in Crohn's disease twins [ p < 0.05]. Conclusion Our results suggest that barrier dysfunction is a primary defect in Crohn's disease, since changes were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems to be a consequence of inflammation, rather than representing a primary defect.
- Publication
Journal of Crohn's & Colitis, 2018, Vol 12, Issue 10, p1200
- ISSN
1873-9946
- Publication type
Article
- DOI
10.1093/ecco-jcc/jjy045