Food-Specific IgG4 Is Associated with Eosinophilic Esophagitis

Rationale: Current forms of allergy testing are unreliable for identifying triggers of eosinophilic esophagitis (EoE). Recent data suggests EoE is IgG4-associated.  We hypothesized that food-specific IgG4 (FS-IgG4) is associated with active EoE and may elucidate dietary triggers.

Methods:  Prospectively collected esophageal biopsies and plasma from 20 EoE subjects (newly diagnosed) and 10 non-EoE controls were tested for total IgG4 (T-IgG4) and FS-IgG4 using ELISA.  After 6-8 weeks of empiric dietary elimination, responder status in EoE subjects was determined by repeat biopsy {diet responders (DR) = 11, non-responders (NR) = 9}. Triggers were identified in DR by elimination, reintroduction, and biopsy.  Follow-up samples were available for 14 EoE subjects (DR = 8, NR = 6).  Comparisons were made between EoE subjects vs. non-EoE controls and DR vs. NR.

Results: Median esophageal T-IgG4 and FS-IgG4 (ng/ml) were significantly elevated in EoE subjects vs. controls (total: 1,847 vs. 469, p = 0.008; peanut: 4.05 vs. 0.01, p = 0.003; soy: 2.12 vs. 0.01, p < 0.001; egg white: 61.4 vs. 2.88, p < 0.001; casein: 55.8 vs. 0.67, p < 0.001; wheat: 19.9 vs. 1.1, p < 0.001).  Esophageal FS-IgG4 correlated with plasma FS-IgG4 for all foods (r > 0.5).  DR demonstrated significant decreases in esophageal T-IgG4 (p = 0.04) and had lower T-IgG4 following dietary elimination compared to NR (673.6 vs. 1,793, p = 0.03).  Importantly, esophageal FS-IgG4 to known triggers also declined significantly in DR (p = 0.02).

Conclusions: Elevated T-IgG4 and FS-IgG4 are associated with active EoE and decline in response to dietary elimination.