Esophageal IgE, IgG4, and mucosal eosinophilia in individuals with dysphagia

Abstract

Background Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, producing failure to thrive in infants and dysphagia with food impaction in older children and adults. Although most people with EoE manifest atopic/allergic disease, the specific allergens to which immunoglobulin E (IgE) is directed, if any, have not yet been characterized. Methods Mucosal brush biopsy (MBB) and solid tissue biopsy (STB) specimens were prospectively obtained from 25 individuals with dysphagia and suspicion of EoE. Specific IgE (sIgE) against 112 epitopes from airborne and food proteins, antigens known to cause a polyclonal IgE response and IgG4 to food allergens, were measured. Results There was no difference in total IgE harvested between the 2 biopsy methods (p > 0.05) or between the EoE‐positive (N = 12) and EoE‐negative (N = 13) groups (p > 0.05). None of the samples in either group contained measurable serum IgE to any of the airborne or food proteins tested, but low levels of IgE specific to Candida and Staphylococcus enterotoxins were detected. Low levels of IgG4 specific to wheat, soy, peanut, and egg were also detected. Conclusions Both MBB and STB are able to harvest measureable levels of IgE and IgG4 from the esophageal mucosa. Low levels of serum‐specific IgE suggest that other inflammatory mechanisms, besides type I, IgE‐mediated, allergen‐specific hypersensitivity, may act as the primary catalyst for mucosal eosinophilia. Clarifying the role of both IgE‐mediated and non‒IgE‐mediated inflammatory mechanisms will help identify more targeted diagnostic and treatment strategies for individuals who present with dysphagia and esophageal eosinophilia.

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

“…For example, Clayton et al identified increased levels of total Immunoglobulin G4 in tissue homogenates from EoE, suggesting that local immune responses occur 18 . Forceps and brush biopsies have revealed that immunoglobulins (Immunoglobulin G4 and Immunoglobulin E) are increased in EoE tissues 21 . Although not studied specifically in EoE, Immunoglobulin A is a known mucosal exclusion antibody secreted on the gastrointestinal surface to protect the body from potential threats, such as bacteria and viruses 22 .…”

British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults

“…One study looking at the efficacy of an antibody against IgE (omalizumab) compared with placebo over 16 weeks147 did not find any benefit, but histological analysis of the oesophageal biopsies showed an increase in IgG-4 in the lamina propria of patients with EoE compared with controls; however the role of IgG-4 in the pathogenesis of EoE remains uncertain. Food-specific IgE/IgG antibodies have been detected in oesophageal samples but the relevance to underlying pathophysiology and management of EoE is unclear 148 149. Targeted dietary elimination on the basis of IgE testing is no more effective than empirical dietary elimination 123 150.…”

Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

“…However, other studies collecting IgG4 directly from the esophageal mucosa showed no differences in the levels of food-specific IgG4 between patients and controls ( Ramaswamy et al, 2019 ) and studies evaluating the efficacy of serum or mucosal IgE or IgG-directed tests in the identification of causal food allergens yielded disappointing results.…”