Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome

Background: The definition of eosinophilic gastritis (EG) is currently limited to histologic EG based on the tissue eosinophil count. Objective: We aimed to provide additional fundamental information about the molecular, histopathologic, and clinical characteristics of EG. Methods: Genome-wide transcript profiles and histologic features of gastric biopsy specimens, as well as blood eosinophil counts, were analyzed in patients with EG and control subjects (n = 15 each). Results: The peak gastric antrum eosinophil count was 283 +/- 164 eosinophils/x400 high-power field in patients with EG and 11 6 9 eosinophils/x400 high-power field in control subjects (P = 6.1 x 10(-7)). Patients with EG (87%) had coexisting eosinophilic inflammation in multiple gastrointestinal segments; the esophagus represented the most common secondary site. Increased peripheral blood eosinophil counts (patients with EG: 1.09 +/- 0.88 x 10(3)/mu L vs control subjects: 0.09 +/- 0.08 10(3)/mu L, P = .0027) positively correlated with peak gastric eosinophil counts (Pearson r(2) = .8102, P < .0001). MIB-1(+) (proliferating), CD117(+) (mast cells), and FOXP3(+) (regulatory T cells, activated T cells, or both) cell counts were increased in patients with EG. Transcript profiling revealed changes in 8% of the genome in gastric tissue from patients with EG. Only 7% of this EG transcriptome overlapped with the eosinophilic esophagitis transcriptome. Significantly increased IL4, IL5, IL13, IL17, CCL26, and mast cell-specific transcripts and decreased IL33 transcripts were observed. Conclusion: EG is a systemic disorder involving profound blood and gastrointestinal tract eosinophilia, T(H)2 immunity, and a conserved gastric transcriptome markedly distinct from the eosinophilic esophagitis transcriptome. The data herein define germane cellular and molecular pathways of EG and provide a basis for improving diagnosis and treatment.