Mast Cells, Eosinophils and Eosinophilic Esophagitis

Abstract

Eosinophilic esophagitis (EoE) is an increasingly recognized disease entity in adults. Studies show a role for eosinophils and mast cells in its pathogenesis. Upper and mid-esophageal biopsy slides from adult patients (n=36) with dysphagia were stained for eosinophil counts (H&E), and immunostained for eosinophil-derived neurotoxin (EDN) and eosinophil major basic protein (MBP). Gene expression was studied by microarray analysis. All patients were consented before the procedure. All research protocols were approved by the Mayo Clinic IRB. EoE patients (n=12; median age 36; 10 male, 2 female) had higher EDN and MBP tissue protein levels as quantified by immunofluorescence. The measured levels of intracellular and extracellular EDN and MBP correlated with eosinophil counts in the EoE patients (median eosinophil count 48±36 cells/high power field (HPF)) compared to controls (n=14; median age 47.2; median eosinophil count 2.8±4 cells/HPF). Genetic microarray analysis showed eotaxin-3 expression was 8-fold higher, eotaxin-2 was 1.3-fold higher, and Charcot-Leyden crystal protein was 2.4-fold higher than controls. For mast cell markers, cathepsin-G precursor expression was 6.2-fold higher, high affinity IgE receptor alpha chain was 2.1-fold higher, carboxypeptidase A3 was 4.5-fold higher, and both cathepsin C and tryptase were 3-fold higher than controls. All fold-changes reached statistical significance (p<0.002). Of note two control patients showed the control phenotype but matched the EoE genotype. The significant increase in eotaxin-3 gene expression in EoE patients is in agreement with previously reported expression levels in children. The increase in mast cell markers supports a role for mast cell involvement in EoE.