Eosinophilic gastrointestinal diseases, or EGIDs, are a group of disorders characterized by dense infiltration of eosinophils in the gastrointestinal tissues. They include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic duodenitis, eosinophilic enteritis, and eosinophilic colitis. In eosinophilic esophagitis, or EoE, food and/or environmental antigens enter through an impaired esophageal epithelial barrier where they stimulate a Th-2-type immune response, with overexpression of Th-2-type cytokines, including eotaxin-3, IL-4, IL-5, and IL-13. These cytokines recruit eosinophils into the esophageal epithelial layer where they degranulate, releasing substances that enhance inflammation, further impairment of barrier function, and fibrosis. Degranulation factors and other cytokines activate other cell types, including mast cells, to perpetuate the inflammatory process. Similar processes are also thought to occur when an EGID involves the stomach, duodenum, or intestines. Monoclonal antibodies are being studied for the treatment of EGIDs. Some monoclonal antibodies target the Th2 inflammatory cytokines IL-4, IL-5, and IL-13. Others target various receptors. An important surface receptor found selectively on mast cells and eosinophils is Siglec-8, which serves as an inhibitory mechanism when activated. Engagement of Siglec-8 by monoclonal antibodies depletes tissue eosinophils through apoptosis and inhibits mast cell activation. As a result, EGID symptoms are diminished.
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