A Novel Allergen-Specific Immune Signature-Directed Approach to Dietary Elimination in Eosinophilic Esophagitis

Abstract

OBJECTIVES: Dietary elimination for treatment of eosinophilic esophagitis (EoE) is limited by lack of accuracy in current allergy tests. We aimed to develop an immunologic approach to identify dietary triggers and prospectively test allergen-specific immune signature-guided dietary elimination therapy. METHODS: In the first phase, we developed and assessed 2 methods for determining selected food triggers using samples from 24 adults with EoE: a CD4+ T-cell proliferation assay in peripheral blood and food-specific tissue IgG4 levels in esophageal biopsies. In the second phase, we clinically tested elimination diets created from these methods in a prospective cohort treated for 6 weeks (NCT02722148). Outcomes included peak eosinophil counts (eos/hpf), endoscopic findings (measured by the EoE Endoscopic Reference Score), and symptoms (measured by the EoE Symptom Activity Index). RESULTS: Parameters were optimized with a positive test on either assay, yielding agreements of 60%, 75%, 53%, 58%, and 53% between predicted and known triggers of peanut, egg, soy, wheat, and milk, respectively. In clinical testing, the mean number of foods eliminated based on the assays was 3.4, and 19 of 22 subjects were compliant with treatment. After treatment, median peak eosinophil counts decreased from 75 to 35 (P = 0.007); there were 4 histologic responders (21%). The EoE Endoscopic Reference Score and EoE Symptom Activity Index score also decreased after treatment (4.6 vs 3.0; P = 0.002; and 32.5 vs 25.0; P = 0.06, respectively). DISCUSSION: We successfully developed a new testing approach using CD4+ T-cell proliferation and esophageal food-specific IgG4 levels, with promising accuracy rates. In clinical testing, this led to improvement in eosinophil counts, endoscopic severity, and symptoms of dysphagia, but a smaller than expected number of patients achieved histologic remission.

Food‐specific antibodies in oesophageal secretions: association with trigger foods in eosinophilic oesophagitis

“…A recent study combined peripheral CD4+ T‐cell proliferation in combination with oesophageal tissue Immunoglobulin G4 food‐specific detection to direct food elimination. The results led to improvement in patients but few with resolution 39 …”

Food allergy as an asthma comorbidity in children and adolescents: a practical approach through a real-world study

“…Eosinophilic esophagitis or gastroenteritis has also been related to FA, and dietary restriction is a common therapeutic approach in these disorders. 34,35 Other biomarkers such as total IgE 36 or FeNO 37,38 can also be modified or influenced by FA.…”

Peripheral markers of allergen‐specific immune activation predict clinical allergy in eosinophilic esophagitis

“…Events were gated by Lymphocytes, Live/Dead negative, CD8 − , CD19 − , CD3 + , CD4 + , CD45RA − , CD45RO + (Figure S2). As food-specific IgG4 levels have been shown to correlate with clinical EoE food allergy, 7,[19][20][21][22] we first examined total and milkspecific IgG4 levels in the plasma of control or clinical EoE milk allergy subjects. We did not observe a significant difference in total IgG4 levels (Figure 1A), but did observe a non-significant increase in milk-specific IgG4 levels in clinical EoE milk allergy subjects compared with controls (Figure 1B).…”

“…While prior studies in animal models and human subjects have shown that allergen-specific T H cells circulate in the blood of patients with EoE, 7,12,14,17 examinations of memory T H -cell populations have not been undertaken. We therefore sought to determine whether We next sought to quantify the extent to which milk-dependent memory T H -cell proliferation associated with clinical EoE milk allergy.…”