Pediatric Eosinophilic Esophagitis Is Associated With Increased Lamina Propria Immunoglobulin G4-Positive Plasma Cells.

Abstract

Eosinophilic esophagitis (EoE) is considered a TH2-mediated food allergy disease that leads to submucosal esophageal fibrosis and strictures. Recent studies focused on adults with EoE identified a strong association with elevated esophageal IgG4 immunostaining. Our study aimed to determine the association of IgG4 with EoE in pediatric patients. Using our local EoE research registry, we identified 41 adequate biopsies from EoE patients. We used 10 age- and sex-matched patients with no diagnostic abnormalities at endoscopy or on biopsy. Using a monoclonal antibody to Immunoglobulin G4 (IgG4), we determined the maximum density of IgG4-positive plasma cells (IgG4-PC) per high-power field (hpf). Using a semi-quantitative assessment, we also graded the noncellular staining of the lamina propria and epithelium. Our EoE cohort consisted predominantly of boys with an average age of 5.9 years and 63% had a documented IgE-based food allergy. Median peak eosinophilia was 40 eosinophils/hpf and the median IgG4-PC density was 39/hpf in the active esophagitis patients, compared with a median of 0 IgG4-PC/hpf in the non-EoE patients (P = 0.0001). EoE patients with a food allergy showed a significantly higher IgG4-PC density (44.5/hpf) than those without a food allergy (8/hpf; P = 0.0385). There was no significant association between IgG4-PC density and peak eosinophilia (r = 0.0011). We demonstrate that active esophagitis in pediatric EoE patients is associated with elevated levels of IgG4-positive plasma cells, which was more significant in EoE patients with a documented food allergy. Our study also adds to the growing literature that EoE may involve more than just an exaggerated TH2 immune response.