Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis

Abstract

Background: Eosinophilic oesophagitis (EO) is an emerging yet increasingly prevalent disorder characterised by a dense and selective eosinophilic infiltration of the oesophageal wall. While EO is considered an atopic disease primarily triggered by food antigens, disparities between standard allergen testing and clinical responses to exclusion diets suggest the participation of distinct antigen-specific immunoglobulin E (IgE) in the pathophysiology of EO. Aim: To find evidence for a local IgE response. Methods: Endoscopic biopsies of the distal oesophagus of atopic and non-atopic EO and control individuals (CTL) were processed for immunohistochemistry and immunofluorescence to assess the presence of B cells, mast cells, and IgE-bearing cells. Oesophageal RNA was analysed for the expression of genes involved in B cell activation, class switch recombination to IgE and IgE production, including germline transcripts (GLTs), activation-induced cytidine deaminase (AID), IgE heavy chain (Cε) and mature IgE mRNA using polymerase chain reaction and microarray analysis. Results: Regardless of atopy, EO showed increased density of B cells (p < 0.05) and of IgE-bounded mast cells compared to CTL. Both EO and CTL expressed μGLT, εGLT, γ4GLT, AID, Cε and IgE mRNA. However, the frequency of expression of total GLTs (p = 0.002), εGLT (p = 0.024), and Cε (p = 0.0003) was significantly higher in EO than in CTL, independent of the atopic status. Conclusion: These results support the heretofore unproven occurrence of both local immunoglobulin class switching to IgE and IgE production in the oesophageal mucosa of EO patients. Sensitisation and activation of mast cells involving local IgE may therefore critically contribute to disease pathogenesis.