Innate Immune Environment in Ileal Pouch Mucosa: α5 Defensin Up-regulation as Predictor of Chronic/Relapsing Pouchitis

Marco Scarpa, Alessia Grillo, Melania Scarpa, Paola Brun, Carlo Castoro, Anna Pozza, Donatella Cavallo, Diego Faggian, Cesare Ruffolo, Renata D'Incà, Romeo Bardini, Ignazio Castagliuolo, Imerio Angriman

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Abstract

Defensins are small cationic peptides with antibacterial activity expressed in Paneth cells (α-defensins) or generally in intestinal epithelial cells (β-defensins) that have a profound effect on gut microbiota. Chronic pouchitis, which occurs in 5% of patients after restorative proctocolectomy and can cause pouch failure, is associated to a significant increase of Clostridiaceae spp. The aim of this study was to gain further insight in the pathogenesis of pouch dysbiosis by exploring defensin expression. Thirty-two consecutive patients coming for follow-up endoscopy were recruited. On pouch biopsies, we cultured bacteria adherent to the mucosa and determined α- and β-defensins and toll-like receptor-4 and -2 mRNA by quantitative real-time RT-PCR. Serum and mucosal levels of IL-1β, IL-6 and TNF-α were measured with immunometric assays. Faecal lactoferrin was analysed by quantitative ELISA. After a median follow-up of 23 (IQR 20-24) months, the patients were contacted for a reassessment of current and past disease activity. During the follow-up, chronic/relapsing pouchitis was diagnosed in six patients. The mucosal level of α-5 and α-6 defensins correlated with chronic/relapsing pouchitis onset (τ = 0. 30, p = 0. 034 and τ = 0. 28, p = 0. 053, respectively). High levels of α-5 defensin resulted to be predictive of chronic/relapsing pouchitis [AUC = 74% (95% CI = 53-89%), p = 0. 052]. Patients with high levels of α-5 and α-6 defensins had earlier pouchitis relapses (p = 0. 009 and p = 0. 034, respectively). High levels of α-5 defensin were associated to a significant risk of chronic/relapsing pouchitis [OR = 10. 6 (95% CI = 1. 2-97. 6), p = 0. 027]. At multivariate analysis, the mucosal levels of α-5 defensin and the number of CFU of mucosa-associated Clostridiaceae spp resulted to be independent predictors of chronic/relapsing pouchitis [β = 0. 46 (0. 18), p = 0. 024 and β = 0. 44 (0. 18), p = 0. 027, respectively]. In conclusion, chronic/relapsing pouchitis is associated to increased expression of mucosal HD-5 and to increased antimicrobial activity against Escherichia coli. In patients with chronic/relapsing pouchitis, HD-5 and TLR-4 over-expression is likely to create a hostile environment against Enterobacteriaceae, thus favouring Clostridiaceae spp by decreasing competing bacteria families.

Original languageEnglish
Pages (from-to)188-202
Number of pages15
JournalJournal of Gastrointestinal Surgery
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 2012

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Keywords

  • Chronic/relapsing pouchitis
  • Defensins
  • Microbiota
  • Restorative proctocolectomy
  • Ulcerative colitis

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

Cite this

Scarpa, M., Grillo, A., Scarpa, M., Brun, P., Castoro, C., Pozza, A., Cavallo, D., Faggian, D., Ruffolo, C., D'Incà, R., Bardini, R., Castagliuolo, I., & Angriman, I. (2012). Innate Immune Environment in Ileal Pouch Mucosa: α5 Defensin Up-regulation as Predictor of Chronic/Relapsing Pouchitis. Journal of Gastrointestinal Surgery, 16(1), 188-202. https://doi.org/10.1007/s11605-011-1720-6