Diagnostic and therapeutic strategies for eosinophilic esophagitis

Abstract

Eosinophilic esophagitis (EoE) is a recently recognized allergic disorder, characterized by eosophageal dysfunction, accumulation of ≥15 eosinophils/high-powered field, eosinophil microabssess, basal cell hyperplasia, extracellular eosinophilic granules in the esophageal epithelial mucosal biopsy and a lack of response to a 8-week proton pump inhibitor treatment. Despite the increased incidences and considerable progress made in understanding EoE pathogenesis, there are limited diagnostic and therapeutic options available for EoE. Currently, the only criterion for diagnosing EoE is repetitive esophageal endoscopic biopsies and histopathological evaluation. Antigen elimination or corticosteroid therapies are effective therapies for EoE but are expensive and have limitations, if continued in the long term. Hence, there is a great necessity for novel noninvasive diagnostic biomarkers that can easily diagnose EoE and assess effectiveness of therapy. Herein, we have provided an update on key molecules involved in the disease initiation, and progression and proposed novel noninvasive diagnostic molecules and strategies for EoE therapy.

Keywords: basophils; eosinophil; esophagitis; interleukin; invariant natural killer T cells; mast cell.

Figure 1. Allergen-induced esophageal eosinophilic esophagitis

APCs process the allergens (food allergens/aeroallergens) and present antigens to T cells (iNKT cells in eosinophilic esophagitis, CD4 T cells in case of other allergic diseases). These T cells home to the esophagus via blood circulation and upon activation release Th2 cytokines (IL-4, IL-13 and IL-5) that induce IL-15 and eotaxin in the esophageal epithelium that attracts eosinophils into the epithelium (≥15 eosinophils/high-powered field). Additionally, in response to allergens, iNKT cells, CD4⁺ T cells, CD8⁺ T cells, B cells, mast cells and basophils are also recruited to the esophagus. B cells synthesize IgE locally or systemically that may activate mast cells and basophils. Basophils and TSLP also contributes to EoE pathogenesis independently of IgE. Activated eosinophils and mast cells secrete TGF-β and other factors that induce esophageal remodeling, including fibrosis, collagen accumulation, muscle cell hyperplasia and epithelial cell hyperplasia that finally cause esophageal dysfunction and lead to eosinophilic esophagitis. APC: Antigen-presenting cell; iNKT: Invariant natural killer T cell; TSLP: Thymic stromal lymphopoietin.