IgG4 Component Allergens Are Preferentially Increased in Eosinophilic Esophagitis As Compared to Patients with Milk Anaphylaxis or Galactose-Alpha-1,3-Galactose Allergy

Rationale: Incidence of food allergy is increasing, including diseases with apparently unique pathophysiologic pathways such as eosinophilic esophagitis (EoE), milk anaphylaxis and galactose-alpha-1,3-galactose (alpha-gal) allergy. The role of IgE in these diseases has been well studied, though the contribution of other antibody subtypes, including IgG4, is less clear.

Methods: Here we assessed IgG4 levels to relevant component allergens from sera banked at the University of Virginia in randomly selected patients carrying diagnoses of EoE, milk anaphylaxis and alpha-gal meat allergy.  IgG4 and IgE levels were measured with ImmunoCap technology using commercial assays or biotinylated antigen coupled to streptavidin immunosorbent.

Results: IgG4 geometric mean levels to milk component allergens Bos d 4 (alpha-lactalbumin) and Bos d 5 (beta-lactoglobulin) were >10 fold higher in EoE patients than milk anaphylaxis or non-allergic controls.  This also correlated with a pronounced shift in the IgE/IgG4 ratio between EoE and milk anaphylaxis.  Similar to the trend seen in milk anaphylaxis but contrary to EoE, alpha-gal patients had marked relative increase in IgE versus IgG4 levels to the relevant allergen galactose-alpha-1,3-galactose.

Conclusions: Levels of IgG4 to relevant allergen are uniquely elevated in EoE as compared to other food allergies, including milk anaphylaxis and alpha-gal, where IgE is the dominant response.  This preliminary work using component-specific testing builds on prior studies demonstrating that IgG4 is preferentially elevated in EoE.  It also highlights that despite a delayed clinical response alpha-gal shares an IgE-to-IgG4 signature similar to other immediate hypersensitivity reactions.