Immunophenotypic Characterization and Quantification of the Epithelial Inflammatory Infiltrate in Eosinophilic Esophagitis Through Stereology: An Analysis of the Cellular Mechanisms of the Disease and the Immunologic Capacity of the Esophagus

Abstract

Eosinophilic esophagitis (EE) is an emerging disease caused by dense infiltration of the esophageal epithelium by eosinophilic leucocytes. It is originated from local hypersensitivity to food or airborne allergens. Although the physiopathologic mechanisms of the illness have not been fully discovered, EE is a loss of immunologic tolerance by the esophagus, meaning that it should be considered as an active immunologic organ. In our study, we investigated the immunologic capacity of the epithelium using immunohistochemistry and stereology, to determine the cellular density of eosinophils, T and B lymphocytes, Langerhans cells, mast cells, and cells manufacturing immunoglobulin E in endoscopic biopsies of patients with EE (taken before and after topical treatment with fluticasone propionate) compared with normal individuals and patients suffering from gastroesophageal reflux disease (GERD). We have observed that the density of eosinophils in EE is 300 times greater than in normal conditions and it is only in this disease where eosinophils show signs of activation and degranulation (positivity to major basic protein immunostaining). The number of T intraepithelial lymphocytes also significantly rose in EE, compared with other entities, where CD8 cells were predominant. However, the human esophagus is deficient in B lymphocytes and we only found intraepithelial plasma cells that excreted immunoglobulin E in EE. Under normal conditions mast cells exist in the thickness of the epithelium that are slightly higher in GERD and multiply in density by 17 in EE. Langerhans cells did not show any significant variation in density under the different tested conditions. After topical treatment with steroids, the density of the different cell components fell to similar levels to GERD. Using our study, we can conclude that the human esophagus may contribute to the development of local immunologic responses as it contains all the necessary cell components. EE represents growth of this esophageal capacity and its pathogeny could respond to mixed cellular and humoral mechanisms.