Esophageal IgG4 and Eosinophilic Inflammation Correlate in Subjects Undergoing Peanut Oral Immunotherapy
Monday, March 5, 2018
South Hall A2 (Convention Center)
Benjamin L. Wright, MD, Matthew A. Rank, MD FAAAAI, Kelly S. Shim, BS, Alfred D. Doyle, PhD, Elizabeth A. Jacobsen, PhD, Monali Manohar, PhD, Bryan J. Bunning, BS, R. Sharon Chinthrajah, MD, Wenming Zhang, PhD, Kari C. Nadeau, MD PhD FAAAAI
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 This trial is ongoing and only the subject with OIT-induced EoE has withdrawn.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.