# Esophageal tissue immunoglobulin G4 in eosinophilic esophagitis and its correlation with serum-specific IgG4 to six foods

## TL;DR

This study shows that high IgG4 levels to casein and egg in blood correlate with worse outcomes in eosinophilic esophagitis patients.

## Contribution

The study identifies a novel correlation between serum IgG4 to specific foods and IgG4-positive plasma cells in esophageal tissue in EoE.

## Key findings

- Patients with IgG4-positive staining had higher endoscopic edema and needed more second-line treatment.
- Serum sIgG4 to milk casein and egg was significantly higher in patients with positive IgG4 staining.
- Higher sIgG4 to casein and egg was linked to worse response to first-line treatment and disease prognosis.

## Abstract

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder in which IgG4 involvement is unclear. We aimed to evaluate immunoglobulin G4 (IgG4) in eosinophilic esophagitis (EoE) and investigate the correlation among IgG4-positive plasma cells in esophageal tissue, total serum immunoglobulin E (IgE), specific IgE, and specific IgG4 (sIgG4) levels to six foods (milk, egg, wheat, soy, peanut, and seafood).

A retrospective observational study with prospective patient inclusion was conducted from 2017 to 2024 in a real-world setting. Clinical, endoscopic, therapeutic, and outcome characteristics of the patients were collected. Positive staining was defined as >10 IgG4-positive plasma cells per HPF. Peripheral blood analyses included measurements of total IgE, specific IgE, and sIgG4.

Seventy-eight patients were included. Patients with positive histological staining exhibited a significantly higher proportion of endoscopic edema (16.1% vs. 2.1%) (p = 0.045; RR = 8.8, 95% CI:1–79.8) and a greater need for second-line treatment (64.5% vs. 41.3%) (p = 0.04; RR = 2.5, 95% CI:1–6.6). Patients with positive IgG4 histological staining exhibited significantly higher median concentrations of serum sIgG4 to milk casein (50.1 mgA/L vs. 11.2 mgA/L; p = 0.005; r = 0.31) and egg (63.4 mgA/L vs. 20.1 mgA/L; p = 0.011; r = 0.28) than those with negative stain. Patients who did not show histological response to first-line treatment had significantly higher concentrations of sIgG4 to casein (31.8 mgA/L vs. 18.6 mgA/L, p = 0.03; r = 0.26) and egg (45.46 mgA/L vs. 19.2 mgA/L, p = 0.03; r = 0.27).

Serum sIgG4 levels to casein and egg were associated with infiltration of IgG4-positive plasma cells in esophageal tissue and a worse disease prognosis.

Flowchart summarizing a study of seventy-eight eosinophilic esophagitis patients showing that elevated serum IgG4 to casein and egg correlates with positive IgG4 histological staining, worse response to first-line treatment, increased endoscopic edema, and greater need for second-line therapy.