title: Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome.
abstract: 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/×400 high-power field in patients with EG and 11 ± 9 eosinophils/×400 high-power field in control subjects (P = 6.1 × 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 × 10(3)/μL vs control subjects: 0.09 ± 0.08 10(3)/μL, 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.
  
  
  CONCLUSIONS
  EG is a systemic disorder involving profound blood and gastrointestinal tract eosinophilia, TH2 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.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Caldwell
authors.affiliation: Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Collins
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Stucke
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Putnam
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: James P
authors.initials: JP
authors.lastname: Franciosi
authors.affiliation: Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Kushner
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Abonia
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: Rothenberg@cchmc.org.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004751:Enteritis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D004802:Eosinophilia / Q000097:blood / Q000276:immunology* / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D008297:Male; D013270:Stomach / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome / Q000276:immunology*
chemical_list: D016207:Cytokines
keywords: CCL26; EG transcriptome; Eosinophilic gastritis; IL-13; eosinophils; mast cells; regulatory T cells