Esophageal IgG4 Levels Are Elevated in Pediatric Eosinophilic Esophagitis and Correlate with Esophageal Histopathology Including Levels of Eosinophils

Recent data suggest an association between elevated levels of IgG4 and adult eosinophilic esophagitis (EoE). Herein, we hypothesize that tissue IgG4 levels are elevated in pediatric subjects with EoE and tissue IgG4 levels correlate with histopathology. A case-control study was performed with pediatric subjects with EoE (≥15 eosinophils/HPF) and non-EoE control subjects. Biopsies obtained for diagnosis were fixed in formalin and scored using the EoE histology scoring system (EoEHSS). Protein isolation/quantitation from additional esophageal biopsies was performed, and samples were diluted to equivalent total protein concentrations (100 μg/mL). IgA, IgM, and IgG1-IgG4 were measured using the Luminex 100 system and IgE was quantified by ELISA. All data were normalized (mg immunoglobulin/g total protein). IgE levels were expressed as IU/mL. Medians were compared using Mann-Whitney U test. Small but significant increases of IgG subclasses, as well as IgA and IgM, were seen in subjects with EoE relative to controls. The highest fold change between groups was seen in IgG4 (3.81 mg/g protein [interquartile range: 0.68-13.07 mg/g protein] vs. 0.30 mg/g protein [interquartile range: 0.06-0.85 mg/g protein]; p=0.0001). A 4.5-fold increase in percent of IgG4 relative to total IgG was observed in EoE biopsies compared to controls (18.0% [interquartile range: 7.5-26.5%] vs. 4.0% [interquartile range: 1.5-7.5%]; p=0.0017). Tissue IgG4 level correlated with peak eosinophil count (p=0.0014) and mean histologic grade (p=0.0063) and stage (p=0.0401) scores. Esophageal IgG4 levels are elevated in pediatric eosinophilic esophagitis and correlate with histopathology including peak eosinophil levels. These data substantiate the involvement of IgG4 in pediatric EoE.