Alpha-defensins (α-Defs) in Crohn's disease: Decrease of ileal α-Def 5 via permanent methylation and increase in plasma α-Def 1-3 concentrations offering biomarker utility

SUMMARY

Background: An impaired expression of α-defensins (α-Defs) in the ileal mucosa and, conversely, increased levels in plasma, have been reported in Crohn's disease (CD). However, the specificity and correlation of these findings with the degree of inflammation are unclear. We aimed to characterize the concentration and utility of ileal and plasma α-Defs in CD and to analyze a potential epigenetic mechanism of α-Def expression.

Methods: Peripheral blood samples and ileal biopsies were obtained from patients at disease onset (aCD), from those who achieved remission (iCD), and from 2 control groups (healthy controls and non-CD-etiology ileitis patients). Plasma α-Defs 1-3 and 4 were detected by ELISA; α-Def 5 by immunolocalization. Methylation analysis of the α-Def 5 gene was performed using the MassARRAY EpiTYPER system.

Results: Plasma α-Defs 1-3 concentrations were significantly higher in aCD with ileal involvement (L1, L3) vs iCD or the control groups. The α-Defs 1-3 concentrations were also similar to healthy controls in patients with non-CD ileitis. There was a significant positive correlation between plasma α-Defs 1-3 levels in aCD and the endoscopic index, as well as with CRP levels. The immunopositivity scoring showed significantly reduced α-Def 5 expression in ileal inflamed (aCD) vs non-inflamed mucosa (iCD and healthy controls). The α-Def 5 gene showed a higher methylation status in CD patients than controls, regardless of the inflammation.

Conclusions: Plasma α-Defs 1-3 concentrations correlate with the degree of inflammation and appear to be specific biomarkers of ileal-CD at diagnosis. Ileal α-Def 5 expression is permanently downregulated by methylation. This article is protected by copyright. All rights reserved.