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. 2023 Mar;53(3):307-315.
doi: 10.1111/cea.14215. Epub 2022 Aug 31.

Food antigen consumption and disease activity affect food-specific IgG4 levels in patients with eosinophilic esophagitis (EoE)

Emily C McGowan  1   2 , Jonathan Medernach  3 , Behnam Keshavarz  1 , Lisa J Workman  1 , Rung-Chi Li  1 , Barrett H Barnes  3 , Bryan Sauer  4 , Jeffrey M Wilson  1 , Thomas A E Platts-Mills  1
Affiliations

Food antigen consumption and disease activity affect food-specific IgG4 levels in patients with eosinophilic esophagitis (EoE)

Emily C McGowan et al. Clin Exp Allergy. 2023 Mar.

Abstract

Introduction: High levels of serum food-specific IgG4 (sIgG4) have been reported in patients with EoE. The objective of this study was to examine whether serum sIgG4 levels to foods and aeroallergens are higher in EoE patients than allergic controls and to investigate the association between sIgG4 and EoE clinical characteristics.

Methods: This was a case-control study nested in a prospective EoE Cohort. EoE cases were defined per consensus guidelines, and controls were individuals with symptoms who were confirmed to be EoE-negative on upper endoscopy. Demographic and clinical information was prospectively collected. Serum IgE and sIgG4 were measured to foods and aeroallergens by ImmunoCAP. Mean levels of sIgG4 were compared between cases and controls, and logistic regression models were used to examine predictors of elevated milk sIgG4 levels.

Results: The analysis included 123 individuals (EoE n = 93, control n = 30) with a similar distribution of allergic disease between EoE patients and controls (86% vs. 93%; p = .30). EoE patients had significantly higher sIgG4 levels to all allergens evaluated, with the exception of birch (p = .24). Milk sIgG4 levels were independently associated with milk consumption (OR 4.95; p = .01) and the presence of sIgE to milk (OR 4.23; p = .008).

Conclusion: Serum sIgG4 levels to food and aeroallergen proteins were higher in patients with EoE than non-EoE controls, and higher levels of milk sIgG4 were independently associated with milk consumption and the presence of sIgE to milk proteins. Whether sIgG4 plays a pathogenic role in EoE or could be used as an EoE biomarker remains unknown and warrants further study.

Keywords: IgE; IgG4; eosinophilic esophagitis (EoE).

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest: J. Medernach, R. Li, B. Keshavarz, and B. Barnes have no potential conflicts of interest. B. Sauer has received a research grant from the American College of Gastroenterology (ACG) and is a consultant with Takeda Pharmaceuticals. E. McGowan has received grants from the National Institutes of Health (NIH), the American Academy of Allergy, Asthma and Immunology (AAAAI), Food Allergy Research and Education (FARE), and the ACG. T. Platts-Mills received research support from Thermo-Fisher/Phadia. J. Wilson received personal fees and research support from Thermo-Fisher/Phadia and is supported by an American Academy of Allergy, Asthma and Immunology (AAAAI) Faculty Development Award.

Figures

Figure 1:
Figure 1:. Food sIgG4 Levels in Subjects with Active EoE and Controls
Food-specific IgG4 levels among patients with active EoE (blue) and non-EoE controls (red). Geometric mean levels are represented by the solid line, and the number of individuals with undetectable levels is listed on the bottom of the graph for each assay. Asterisks represent p<0.001 (****) and p<0.05 (**).
Figure 2:
Figure 2:. Aeroallergen sIgG4 Levels in Subjects with Active EoE and Controls
Aeroallergen-specific IgG4 levels among patients with active EoE (blue) and controls (red). Geometric mean levels are represented by the solid line, and the number of individuals with undetectable levels is listed on the bottom of the graph for each assay. Asterisks represent p<0.001 (****) and p<0.05 (**).
Figure 3:
Figure 3:. Cumulative Milk sIgG4 Levels Stratified by Milk Consumption
Milk-specific IgG4 levels (sum of Bos d 4, 5, and 8) among non-EoE control patients (red) and active EoE (blue), stratified by milk consumption. Geometric mean levels are represented by the solid line.
Figure 4:
Figure 4:. Paired Food sIgG4 Measurements in Active Disease and Remission
Food-specific IgG4 levels in paired samples collected from EoE patients with active disease and remission. Remission in these patients was achieved by adding a swallowed steroid, and patients were instructed to not change consumption of potential trigger foods (milk, wheat, egg, or soy) between the two endoscopies.
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