Molecular, genetic, and cellular bases for treating eosinophilic esophagitis

Gastroenterology. 2015 May;148(6):1143-57. doi: 10.1053/j.gastro.2015.02.002. Epub 2015 Feb 7.

Abstract

Eosinophilic esophagitis (EoE) was historically distinguished from gastroesophageal reflux disease on the basis of histology and lack of responsiveness to acid suppressive therapy, but it is now appreciated that esophageal eosinophilia can respond to proton pump inhibitors. Genetic and environmental factors contribute to risk for EoE, particularly early-life events. Disease pathogenesis involves activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]), impaired barrier function (mediated by loss of desmoglein-1), increased production and/or activity of transforming growth factor-β, and induction of allergic inflammation by eosinophils and mast cells. Susceptibility has been associated with variants at 5q22 (TSLP) and 2p23 (CAPN14), indicating roles for allergic sensitization and esophageal specific protease pathways. We propose that EoE is a unique disease characterized by food hypersensitivity; strong hereditability influenced by early-life exposures and esophageal-specific genetic risk variants; and allergic inflammation and that the disease is remitted by disrupting inflammatory and T-helper type 2 cytokine-mediated responses and through dietary elimination therapy.

Keywords: Allergy; Barrier; Cytokines; Diagnostics; Eosinophils; Epithelium; Esophagitis; Genetics; Therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Allergens / adverse effects
  • Animals
  • Calpain / genetics
  • Calpain / immunology
  • Cytokines / genetics
  • Cytokines / immunology
  • Diet / adverse effects
  • Environment
  • Eosinophilic Esophagitis / diagnosis
  • Eosinophilic Esophagitis / diet therapy*
  • Eosinophilic Esophagitis / genetics*
  • Eosinophilic Esophagitis / immunology
  • Food Hypersensitivity / diagnosis
  • Food Hypersensitivity / diet therapy*
  • Food Hypersensitivity / genetics*
  • Food Hypersensitivity / immunology
  • Gene Expression Regulation
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Heredity
  • Humans
  • Molecular Diagnostic Techniques
  • Phenotype
  • Precision Medicine
  • Predictive Value of Tests
  • Risk Factors
  • Th2 Cells / immunology

Substances

  • Allergens
  • Cytokines
  • Genetic Markers
  • Calpain
  • thymic stromal lymphopoietin