Changes in IgG4 and IL-10 expression in adults with eosinophilic esophagitis on a two-food elimination diet

Abstract

Background: Eosinophilic esophagitis (EoE) is increasingly diagnosed in patients with dysphagia and upper gastroenteric symptoms. Elimination diets and/or pharmacologic agents may accomplish temporary remission, but long-term control is challenging. Type-2 immunity to ingested antigens can induce EoE histopathology via non-IgE-dependent mechanisms, possibly involving IgG4 and IL-10 production. To elucidate the contribution of IgG4- and IL-10-producing cells to EoE pathogenesis, we examined their frequencies and association with clinical and histologic endpoints in adult EoE patients given a two-food elimination diet (TFED). Methods: Sixteen patients with EoE were prescribed a TFED. Biopsies collected at baseline and follow-up were used for immunofluorescent detection of IgG4- and IL-10-expressing cells and serum food-specific IgG4 were measured. All variables were correlated with established histologic measures of disease activity. Results: Patients exhibited significant clinical improvement and significant reduction in esophageal eosinophilia and overall histology. A significant decrease in the frequencies of IL-10-expressing cells was also observed, which correlated with histologic changes. In contrast, a concomitant decline in serum and esophageal IgG4, while substantial, did not correlate with IL-10 -cell frequencies or any histologic parameter of EoE activity. Conclusions: The close association of esophageal IL-10 expression with histologic features and their changes after a TFED suggests a critical role of this cytokine in EoE pathogenesis. Conversely, IgG4 serum and mucosal expression, while reflecting the level of exposure to relevant food antigens, is not obviously related to EoE histopathology or IL-10 expression. Studies are needed to characterize IL-10 cellular sources and their functions in EoE progression and treatment response.