Abstract
BackgroundOral food challenge using gluten and cofactors is the gold standard to diagnose wheat‐dependent exercise‐induced anaphylaxis (WDEIA), but this procedure puts patients at risk of an anaphylactic reaction. Specific IgE to ω5‐gliadins as major allergens and skin prick tests to wheat may yield negative results. Thus, we designed a proof‐of‐principle study to investigate the utility of the basophil activation test (BAT) for WDEIA diagnosis.MethodsDifferent gluten protein types (GPT; α‐, γ‐, ω1,2‐ and ω5‐gliadins, high‐molecular‐weight glutenin subunits [HMW‐GS] and low‐molecular‐weight glutenin subunits [LMW‐GS]) and gluten were used in different concentrations to measure basophil activation in 12 challenge‐confirmed WDEIA patients and 10 control subjects. The results were compared to routine allergy diagnostics. Parameters analyzed include the percentage of CD63+ basophils, the ratio of %CD63+ basophils induced by GPT/gluten to %CD63+ basophils induced by anti‐FcεRI antibody, area under the dose‐response curve and test sensitivity and specificity.ResultsGPT and gluten induced strong basophil activation for %CD63+ basophils and for %CD63+/anti‐FcɛRI ratio in a dose‐dependent manner in patients, but not in controls (p < 0.001, respectively). BAT performance differed from acceptable (0.73 for LMW‐GS) to excellent (0.91 for ω5‐gliadins) depending on the specific GPT as evaluated by the area under the receiver operating characteristic curve. Patients showed individual sensitization profiles. After determination of the best cut‐off points, ω5‐gliadins and HMW‐GS showed the best discrimination between patients and controls with a sensitivity/specificity of 100/70 and 75/100, respectively.ConclusionThis study shows the alternative role of BAT in better defining WDEIA and the causative wheat allergens. The best BAT parameters to distinguish WDEIA patients from controls were %CD63+ basophil values for ω5‐gliadins and HMW‐GS.
Highlights
Wheat‐dependent exercise‐induced anaphylaxis (WDEIA) is a rare, but potentially life‐threatening cofactor‐induced wheat allergy. ω5‐ gliadins and high‐molecular‐weight glutenin subunits (HMW‐GS) are most often reported as major allergens, but reactions to other gluten protein types (GPTs) from wheat, like low‐molecular‐weight glutenin subunits (LMW‐GS), α‐ and γ‐gliadins were described
Even specific IgE (sIgE) to ω5‐gliadins are only positive in about 80% of wheat‐dependent exercise‐induced anaphylaxis (WDEIA) patients, indicating that other GPT play a role in WDEIA
Significantly higher in patients compared to controls (p < 0.001), but there were no significant differences for ω1,2‐gliadins, γ‐gliadins, LMW‐GS, and gluten (p > 0.05)
Summary
Wheat‐dependent exercise‐induced anaphylaxis (WDEIA) is a rare, but potentially life‐threatening cofactor‐induced wheat allergy. ω5‐ gliadins and high‐molecular‐weight glutenin subunits (HMW‐GS) are most often reported as major allergens, but reactions to other gluten protein types (GPTs) from wheat, like low‐molecular‐weight glutenin subunits (LMW‐GS), α‐ and γ‐gliadins were described. BAT‐derived parameters such as the percentage of basophils that respond to a given dose of the ATS or the area under the curve (AUC) of a dose‐response curve have been shown to be sensitive biomarkers corresponding to the clinical severity of anaphylactic reactions.[8,9] The BAT has been established for the identification of different immediate allergies, like allergy against wheat,[8,10] hymenoptera venom,[11] and alpha‐galactose.[12] The aim of this proof‐of‐principle study was to investigate the utility of the BAT to improve WDEIA diagnosis and to determine individual sensitization profiles in WDEIA patients to different isolated and well‐characterized GPT and gluten. Details of the production and characterization of GPT can be found in the Supporting Methods
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