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Gut barrier dysfunction: a primary defect in twins with Crohn's disease predominantly caused by genetic predisposition
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Örebro universitet, Institutionen för medicinska vetenskaper. Department of Medical Sciences.
Department of Pathology and Cytology, Aleris Medilab, Täby, Sweden.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
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2018 (Engelska)Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, nr 10, s. 1200-1209Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 if 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 increased 51Cr-EDTA permeability at 120 min both with Acetylsalicylic acid (p<0.001) and without (p<0.001) when compared to controls. A significant increase in 51Cr-EDTA flux was seen already at 20 minutes in healthy monozygotic co-twins compared to 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 to 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.

Ort, förlag, år, upplaga, sidor
Elsevier, 2018. Vol. 12, nr 10, s. 1200-1209
Nyckelord [en]
Crohn's disease, barrier function, genetics
Nationell ämneskategori
Gastroenterologi
Identifikatorer
URN: urn:nbn:se:oru:diva-66791DOI: 10.1093/ecco-jcc/jjy045ISI: 000455271000008PubMedID: 29659773Scopus ID: 2-s2.0-85056415292OAI: oai:DiVA.org:oru-66791DiVA, id: diva2:1201947
Forskningsfinansiär
Vetenskapsrådet, VR-MH 2014-02537 521-2011-2764
Anmärkning

Funding Agency:

Region Östergötland, ALF research funds of Linköping University 

Tillgänglig från: 2018-04-27 Skapad: 2018-04-27 Senast uppdaterad: 2019-12-20Bibliografiskt granskad

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Lindqvist, Carl MårtenSchoultz, IdaHalfvarson, Jonas

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