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RATIONALE: Food allergy, impaired mucosal barrier function and abundant local IgG4 production have all been described in eosinophilic esophagitis (EoE). We investigated IgG4 to multiple food antigens that are implicated in EoE, as well as desmoglein 1 and 3 based on their role in mucosal barrier function and as established IgG4 targets in variants of pemphigus. METHODS: We assessed IgG4 levels to relevant food antigens from sera banked at the University of Virginia in randomly selected pediatric and adult patients with biopsy-diagnosed EoE and relevant controls. IgG4 and IgE were measured by ImmunoCAP using commercial assays or biotinylated antigen coupled to streptavidin immunosorbent. For desmoglein 1 and 3, we screened sera from 10 adult and 10 pediatric EoE patients using a modified commercially available ELISA. RESULTS: IgG4 geometric mean levels to multiple food antigens represented in the six-food elimination diet were significantly higher in EoE patients as compared to relevant allergic and non-allergic controls. The milk proteins alpha-lactalbumin, beta-lactoglobulin and caseins were the most pronounced. Significant, but less strong results were obtained for IgG4 to egg proteins ovalbumin and ovomucoid. IgG4 to galactose-alpha-1,3-galactose was undetectable or <1% of the total IgG4 in EoE patients and controls. IgG4 signatures were similar in both pediatric and adult cohorts. There was no evidence of serum IgG4 to desmoglein 1 or 3. CONCLUSIONS: IgG4 to milk proteins are elevated in EoE compared to non-allergic controls and traditional IgE-mediated food allergies. Desmoglein down-regulation has been described in EoE but we saw no evidence that the mechanism involves IgG4 autoantibodies.

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