Oesophageal secretions reveal local food‐specific antibody responses in eosinophilic oesophagitis

Abstract

Background: Eosinophilic oesophagitis (EoE) is associated with elevated IgG4 in oesophageal tissue and serum. Previously, we showed brush-collected oesophageal secretions of EoE patients contained food antigen-specific antibodies IgA and IgG4. It is unknown whether other food-specific antibodies are present along the surface of the oesophagus in EoE. Aim: To identify whether immunoglobulins other than IgG4 and food-specific antibodies are elevated along the oesophageal mucosal surface in oesophageal secretions in EoE patients Methods: Concentrations of total IgA, IgG1, IgG2, IgG3, IgG4, IgM and IgE were measured in oesophageal secretions from patients with active (n = 19) and inactive EoE (n = 9), and non-EoE controls (n = 10). Food-specific antibodies were measured using beads coupled to protein components from dairy, wheat and egg. Total immunoglobulin and cytokine and chemokine concentrations were measured in serum, saliva and oesophageal secretions of four patients with active EoE. Results: Oesophageal secretions have a unique immune profile. Patients with active EoE had elevated IgG2, IgG4 and IgM concentrations in oesophageal secretions compared to those with inactive EoE. Food-specific IgG1, IgG2, IgG4 and IgM were significantly increased in patients with active EoE compared to inactive EoE and non-EoE patients. Furthermore, active patients with a known dairy trigger display higher dairy-specific IgG1, IgG2, IgG4, IgM, IgA and IgE.Conclusions: There is a distinct localised profile of immunoglobulins and foodspecific antibodies found within oesophageal secretions in EoE. These findings expand our knowledge about the currently identified immune responses in EoE and suggest possible roles for multiple immunoglobulins and food-specific antibodies in the pathophysiology of EoE.

Non-Invasive and Minimally Invasive Biomarkers for the Management of Eosinophilic Esophagitis beyond Peak Eosinophil Counts: Filling the Gap in Clinical Practice

“…Recent randomized controlled trials have questioned the utility of peak eosinophil counts as a clinically meaningful endpoint in EoE [89,90]. In this regard, in two recent randomized controlled trials on novel biological drugs for EoE, namely the MESSINA (benralizumab) and KRYPTOS (lirentelimab) studies, most patients taking active treatment achieved histological remission, but the drugs failed to induce a significant improvement in symptoms compared to placebos [81,82]. In addition, a recent study comparing patients with symptomatic to patients with asymptomatic esophageal eosinophilia suggested that mast cells may contribute to the perception of symptoms in EoE, highlighting the possible role of other non-eosinophil-derived biomarkers in EoE [52].…”

“…Additionally, it has been shown that EoE treatment may have an effect on mucosal IgG4s, as a significant decrease in esophageal IgG4s has been observed following the successful treatment of EoE [54]. More recently, Pyne et al [81] showed that patients with active EoE had elevated IgG2, IgG4, and IgM in esophageal luminal secretions compared to those with inactive EoE. In addition, the authors also found that food-specific IgG1, IgG2, IgG4, and IgM were significantly increased in patients with active EoE compared to EoE in remission.…”

Changes in IgG4 and IL-10 expression in adults with eosinophilic esophagitis on a two-food elimination diet

“…Increased levels of milk and wheat sIgG4 have been found in the esophageal secretions from active EoE. 31,47 Preferential uptake of milk antigens was seen in the adult EoE mucosa, whereas gliadin penetration was more critically dependent on barrier perturbation and disease activity. 48 Thus, IgG4 production in response to distinct milk or wheat components may follow diverging trajectories and associate with distinct clinical phenotypes, as shown in IgE-dependent conditions.…”