Esophageal IgG4 and Eosinophilic Inflammation Correlate in Subjects Undergoing Peanut Oral Immunotherapy

Rationale: Peanut oral immunotherapy (PN-OIT) is associated with increases in serum peanut-specific IgG4. Recent studies suggest that eosinophilic esophagitis (EoE), a potential complication of PN-OIT, is associated with marked tissue deposition of IgG4. We sought to examine the IgG4 and eosinophil responses to PN-OIT in gastrointestinal biopsies.

Methods: We performed serial esophagogastroduodenoscopies (EGD) in adults undergoing PN-OIT. Biopsies were obtained from the esophagus, stomach, and duodenum at baseline, 1, and 2yrs. Immunohistochemical staining for IgG4 and eosinophil peroxidase (EPX) were performed. Deposition of IgG4/mm² and EPX/mm² in serial hpf were quantified using automated image analysis.

Results: EGD’s were performed at baseline (n = 21), 1yr (n = 10) and 2yrs (n = 5) during PN-OIT. At baseline, 48% of subjects had gastrointestinal eosinophilia (esophagus ≥15 eos/hpf; stomach ≥30 eos/hpf; and duodenum (≥52 eos/hpf). EPX/mm² correlated strongly with eos/hpf in all biopsies (r = 0.89, p < 0.0001) and with IgG4/mm² at baseline (r = 0.38, p = 0.004), 1yr (r = 0.36, p = 0.05) and 2yrs (r = 0.72, p = 0.003). Importantly 4/8 subjects with <15 eos/hpf at baseline developed esophageal eosinophilia; one met clinicopathologic criteria for EoE and 2 had histologic resolution by 2yrs. This trial is ongoing and only the subject with OIT-induced EoE has withdrawn.

Conclusions: This is the first study examining tissue IgG4 deposition in serial gastrointestinal biopsies (including baseline) during PN-OIT. Similar to EoE, PN-OIT subjects demonstrate esophageal IgG4 deposition correlating with eosinophilic inflammation. Further studies are needed to clarify the relationship between IgG4, EoE, and PN-OIT.