Circulating Food Allergen‐Specific Antibodies, Beyond IgG4, Are Elevated in Eosinophilic Esophagitis

IntroductionEosinophilic esophagitis (EoE) is a chronic inflammatory condition with an incompletely understood immuno‐pathogenesis involving a T2 response. EoE is triggered by food allergens although, unlike IgE‐mediated allergies, it exhibits high IgG4 levels in oesophageal biopsies and in circulation. We investigated whether other antibody isotypes specific for food allergens are elevated in EoE and vary with disease activity.MethodsPlasma samples from patients with active EoE (n = 51), inactive EoE (n = 82) and non‐EoE controls (n = 14) were analysed for food‐specific IgG and IgA subclasses against casein, whey, wheat, egg and individual cow's milk allergens by ELISA. α‐lactalbumin (Bos d 4)‐ and β‐lactoglobulin (Bos d 5)‐specific B cells were measured by flow cytometry in a subset of patients.ResultsFood allergen‐specific antibodies in the plasma varied across EoE subgroups and non‐EoE controls. Elevated IgG4 in EoE patients confirmed a strong antibody response to food allergens, including casein, wheat and egg. α$_{S1}$‐casein (Bos d 9)‐specific IgG, IgG2, IgG4, IgA1 and IgA2 differed between EoE and non‐EoE controls and between active and inactive EoE. β‐casein (Bos d 11, A1 variant) measurements showed higher levels of specific IgG2 and IgG4 in both EoE groups, whereas whey‐derived allergens showed opposing responses: Bos d 4 responses favoured IgG4, and Bos d 5 responses were elevated across multiple IgG and IgA subclasses in EoE. Allergen‐specific B cells could not be isolated from the circulation.ConclusionOur findings reveal distinct antibody profiles in EoE plasma, with elevated IgG and IgA subclasses beyond IgG4, highlighting a complex immune response to food allergens. Differential antibody responses support their clinical relevance in dietary management strategies, while the absence of allergen‐specific B cells in circulation likely restricts antibody production to the inflamed oesophagus. Future research should explore whether these antibody profiles can guide personalised treatment and novel therapeutic targets in EoE.