Local type 2 immunity in eosinophilic gastritis

Abstract

Eosinophilic gastritis (EoG) associates with type 2 immunity. However, the type 2 cytokine cellular source, gastric T-cell composition, and gastric T-cell relationship (or relationships) with disease pathology remain understudied. We defined gastric T-cell populations and their association with histologic and endoscopic EoG pathology. Gastric biopsy samples (n= 6 EoG, n= 7 control) were subjected to histologic, endoscopic, and flow cytometry analyses. In a complementary cohort (n= 83 EoG), IL4, IL5, and IL13 mRNA levels were correlated with EoG pathologic parameters. Gastric biopsy samples contained CD3+ T cells that were mainly CD8+; the CD8/CD4 ratio was comparable in EoG and control biopsy samples (5.7± 3.0 and 4.3± 0.6, respectively; P= .28). Gastric regulatory T (CD3+CD4+FOXP3+) and TH2 (CD3+CD4+GATA3+) cell levels were increased in EoG versus controls (2-fold, P< .05 and 10-fold, P< .001, respectively) and correlated with gastric eosinophil levels (r= 0.63, P< .05 and r=0.85, P< .001, respectively), endoscopic pathology (r= 0.56, P< .01; r= 0.84, P< .001, respectively), and histopathology (r= 0.72,P< .01; r= 0.82, P< .01, respectively). Cytokine-positive, most notably IL-4+, TH2 cell levels strongly correlated with histologic and endoscopic scores (r= 0.82, P< .0001 and r=0.78, P< .0001, respectively). In an independent EoG cohort (n= 83), bulk gastric IL4, IL5, and IL13 mRNA levels correlated with histologic score (r= 0.22, P< .005; r= 0.54, P< .0001; and r= 0.36, P< .0001, respectively) and endoscopic score (r= 0.27, P< .001; r= 0.40, P< .0001; and r= 0.35, P< .0001, respectively). EoG is a TH2 cell-associated disease featuring increased gastric type 2 cytokine-producing CD3+CD4+GATA3+TH2 cells that strongly correlate with disease pathologies.