Oesophageal Secretions Reveal Local Food-specific Antibody Responses in Eosinophilic Oesophagitis

Ashley L. Pyne; Mark W. Hazel; Amiko M. Uchida; Fares Qeadan; Kristine C. Jordan; Amy Holman; Brinnlie Harward; Gerald J. Gleich; Kathryn A. Peterson

Disclosures

Aliment Pharmacol Ther. 2022;56(9):1328-1336. 

In This Article

Abstract and Introduction

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 food-specific 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.

Introduction

Eosinophilic oesophagitis (EoE) is a chronic type 2 immune-mediated disease of the oesophagus, triggered primarily by food antigens and resulting in oesophageal eosinophilia, difficulty in swallowing and decreased quality of life.[1] While the pathogenesis of EoE remains incompletely understood, elimination diets show that food allergens (dairy, gluten, egg, soy, peanut/tree nut and fish/shellfish) are the most common triggers, suggesting that an antigen-specific immune response is important for EoE.[2–4]

The nature of the immunoglobulin responses to food and the role in EoE pathogenesis remains incompletely understood. However, we know T helper 2 (Th2) inflammatory cytokines interleukin (IL)-4 and IL-13 are crucial for EoE pathogenesis and promote B-cell isotype switching to immunoglobulin (Ig)E, IgG1 and IgG4.[5,6] Additionally, vaccine studies demonstrate that facilitating a Th2 inflammatory environment can elicit robust mucosal IgA along with serum IgG1, IgG2 and IgE.[7] Within oesophageal tissue extracts, total IgG subclasses, IgA and IgM are significantly increased in paediatric patients with active EoE, with the greatest increase in IgG4.[8] IgG4 is also elevated in the serum of patients with EoE.[9] Furthermore, food-specific IgG4 levels are significantly elevated in the serum and oesophageal tissue of patients with EoE,[10–12] suggesting IgG4 plays a key role in pathogenesis. However, immunoglobulin profiling using oesophageal tissue biopsy extracts is limited in EoE due to the patchy involvement of the disease in tissue. To increase sampling area, oesophageal brushings of the oesophageal mucosa surface can be performed to collect oesophageal secretions (oES). Previously oES analyses demonstrated that patients with active EoE had increased IgA and IgG4 antibodies in oES to casein, gluten, soy and egg compared to patients in disease remission.[13] Thus, oES be used to measure the local oesophageal immune responses that demonstrate food specificity in EoE.

We aimed to expand upon our prior work to characterise which immunoglobulins and food-specific antibodies (FSAs) are present in EoE. We found that total immunoglobulin isotypes and subclasses in oES distinguish patients with active EoE from patients with inactive EoE. Furthermore, we identified that oES contain food-specific antibodies which are specific to active EoE.

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