Abstract
Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a cofactor-induced wheat allergy. Gluten proteins, especially ω5-gliadins, are known as major allergens, but partially hydrolyzed wheat proteins (HWPs) also play a role. Our study investigated the link between the molecular composition of gluten or HWP and allergenicity. Saline extracts of gluten (G), gluten with reduced content of ω5-gliadins (G-ω5), slightly treated HWPs (sHWPs), and extensively treated HWPs (eHWPs) were prepared as allergen test solutions and their allergenicity assessed using the skin prick test and basophil activation test (BAT) on twelve patients with WDEIA and ten controls. Complementary sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE), high-performance liquid chromatography (HPLC), and mass spectrometry (MS) analyses revealed that non-gluten proteins, mainly α-amylase/trypsin inhibitors (ATIs), were predominant in the allergen test solutions of G, G-ω5, and sHWPs. Only eHWPs contained gliadins and glutenins as major fraction. All allergen test solutions induced significantly higher %CD63+ basophils/anti-FcεRI ratios in patients compared with controls. BAT using sHWPs yielded 100% sensitivity and 83% specificity at optimal cut-off and may be useful as another tool in WDEIA diagnosis. Our findings indicate that non-gluten proteins carrying yet unidentified allergenic epitopes appear to be relevant in WDEIA. Further research is needed to clarify the role of nutritional ATIs in WDEIA and identify specific mechanisms of immune activation.
Highlights
Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a cofactor-induced wheat allergy
A positive reaction was triggered in all patients with WDEIA for G (W/E 6.1 and 15.4 mm), in 11 of 12 patients for slightly treated HWPs (sHWPs) (W/E 5.8 and 13.7 mm), in 10 of 12 patients for G-ω5 (W/E 3.8 and 7.0 mm), and in 9 of 12 patients for extensively treated HWPs (eHWPs) (W/E 6.2 and 11.1 mm) (Figure 1 and Supplementary Table 2)
skin prick test (SPT) results showed that wheal and erythema diameters caused by G-ω5 were the lowest compared with other substances, but the differences were not significant except for the comparison of erythema diameter between G and G-ω5
Summary
Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a cofactor-induced wheat allergy. In Japanese adolescents, the prevalence of food-dependent exerciseinduced anaphylaxis predominantly to wheat was 0.017%. As these patients tolerate wheat in the absence of association with cofactors, WDEIA may not be recognized in many patients and they are often given the diagnosis of idiopathic anaphylaxis instead [1,2,3]. Patients with WDEIA may react to intact gluten proteins and/or partially hydrolyzed wheat proteins (HWPs) [4,5,6]. HWPs are made of gluten subjected to chemical or enzymatic partial hydrolysis to obtain foaming and emulsifying properties for use in foods and cosmetics [6, 8, 9]. The increase in solubility of HWPs compared with native gluten affects allergen passage through the skin or the small intestine [6, 7, 13]
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