Gene expression-phenotype associations in adults with eosinophilic esophagitis

Background: Gene expression patterns have not been extensively examined in the context of clinical features of eosinophilic esophagitis (EoE). Aims: To assess whether gene expression is associated with clinically defined phenotypes in adults with EoE. Methods: This was an analysis of prospectively collected esophageal biopsies in newly diagnosed EoE patients. We determined differential gene expression with a 94 gene panel in relation to clinical features and phenotypes. These included: endoscopic findings of esophageal rings, stricture, narrowing, linear furrows, exudates, edema, and dilation; an allergic phenotype; an inflammatory phenotype, and a fibrostenotic phenotype. Results: In 89 EoE cases analyzed, patients with exudates on endoscopy had multiple differences in gene expression compared to patients without exudates, though patients with exudates also had higher eosinophil counts (172 vs 106 eos/hpf; p =.01). Genes associated with esophageal narrowing included CCL26 (q-value = 0.028), ALOX15 (q = 0.011), GRK5 (q = 0.029), CPA3 (q = 0.012), and TRIM2 (q = 0.0027). TRIM2 was also associated with the fibrostenotic phenotype (q = 0.0051). No genes were associated with the inflammatory or atopic phenotypes, or with dilation. Conclusions: Multiple genes are associated with exudates, possibly related to higher eosinophil counts. However, a number of genes, including those related to both inflammation and remodelling, are associated with esophageal narrowing. In particular, TRIM2 is associated with clinical fibrotic phenotypes.