Epithelial Markers Can Reflect Esophageal Fibrosis Score in Pediatric Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) pathogenesis includes subepithelial fibrosis of the lamina propria (LP). Fibrosis can be scored semi-quantitatively with a fibrosis score. While fibrosis is thought to reflect disease severity, not all biopsies contain adequate LP for analysis. We have previously shown that PAI-1 is part of the EoE fibrotic cascade. Immunohistological patterns of epithelial staining for plasminogen activator inhibitor-1 (PAI-1) and tryptase in the esophageal epithelium were investigated as potential markers of fibrotic severity. Esophageal tissue biopsies from children with active and inactive EoE and from normal esophagi were stained with PAI-1 and tryptase (n=41 PAI-1, n=57 tryptase). We quantified the degree of active staining in the epithelium using Image J. The relationship between PAI-1, tryptase, and fibrosis scores was evaluated. Epithelial PAI-1 was significantly higher in active versus inactive EoE (p < .001) and discriminated between fibrosis scores of 0 or 1 versus 3 and fibrosis score of 1 versus 2 (p < .05 for each). Tryptase was significantly higher in active versus inactive EoE (p < .0001) and differentiated between fibrosis score of 0 versus 1, 2, or 3 and a score of 1 versus 3 (p < .05 for each). PAI-1 and tryptase correlated with fibrosis scores (r = 0.62 and 0.76, respectively, p < .0001). Epithelial staining patterns for PAI-1 and tryptase distinguish distinct groups of fibrotic severity and poses a way to gauge the potential severity of EoE in a patient through immunohistochemistry of the epithelium.