Background: Eosinophilic esophagitis (EE) is an emerging yet increasingly prevalent disorder characterized by a dense and selective eosinophilic infiltration of the esophageal wall. While EE 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 IgE in the pathophysiology of EE.
Aim: To find evidence for a local IgE response.
Methods: Endoscopic biopsies of the distal esophagus of atopic and nonatopic EE and control individuals (CTL)were processed for immunohistochemistry and immunofluorescence to assess the presence of B cells, mast cells, and IgE-bearing cells. Esophageal RNA was analyzed for the expression of genes involved in B cell activation, class switch recombination to IgE and IgE production, including germline transcripts (GLT), activation-induced cytidine deaminase (AID), IgE heavy chain (C∊) and mature IgE mRNA using PCR and microarray analysis.
Results: Regardless of atopy, EE showed increased density of B cells (P<0.05) and of IgE-bounded mast cells compared to CTL. Both, EE and CTL, expressed μGLT, ∊GLT, γ4GLT, AID, C∊ and IgE mRNA. However, the frequency of expression of total GLT (P=0.002), ∊GLT (P=0.024), and C∊(P=0.0003) was significantly higher in EE 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 esophageal mucosa of EE patients. Sensitization and activation of mast cells involving local IgE may therefore critically contribute to disease pathogenesis.