Differing Epithelial and Immunologic Activation Patterns Following Food Reintroduction Reveal Differential Transcriptional Profiles in Active Eosinophilic Esophagitis

During food trigger reintroductions, eosinophilia can recur in a patchy manner both endoscopically and histologically. We postulated that areas containing low eosinophils represented the early stage of EoE recurrence, while areas with >15 eos/HPF represented established active EoE. We identified ten patients with prior pan-esophageal EoE who experienced patchy eosinophilia during trigger food reintroduction. The progression of recurrent EoE is illustrated by the transcriptional changes occurring from baseline remission through recurrent low and high eosinophil tissues in those with paired time points. We identified novel genes of cytokine regulation distinct to the low eosinophil tissue, indicating involvement of such cytokines before the onset of diagnostic eosinophilic infiltration. The advancement to robust eosinophil is associated with more severe epithelial injury in conjunction with further inflammation. Utilization of a food antigen re-exposure model elucidates immunological and epithelial changes that instigate and perpetuate the development of EoE. To investigate transcriptional shifts associated with the elimination and reintroduction of an antigen. Formalin-fixed, paraffin-embedded esophageal biopsies from patients with EoE at paired time points: (1) “baseline remission” with trigger foods eliminated (n=5, <10 eos/HPF); (2) trigger food reintroduction with patchy eosinophilia consisting of (2a) “recurring low eosinophil” (n=10, <13 eos/HPF) and (2b) “recurring high eosinophil” (n=10, >18 eos/HPF). Non-EoE control esophageal samples (n=22) were included from patients with normal histology.