A novel wheat gliadin as a cause of exercise-induced anaphylaxis

Background: Food-dependent, exercise-induced anaphylaxis is a severe form o f allergy; the reaction is caused by ingestion of a specific food before ex ercise. This disorder often escapes diagnosis because neither the ingested food nor the exercise alone induces the symptoms. Objective: The aim of the study was to characterize the allergens involved in wheat-dependent, exercise-induced anaphylaxis and to describe the clinic al outcome in a series of 18 adult patients. Methods: All 18 patients had experienced recurrent episodes of generalized urticaria during exercise, 17 patients in association with collapse and 15 patients with an anaphylactic reaction. The symptoms appeared only when the patients had eaten food containing wheat before exercise. Wheat allergens were detected by immunoblotting, purified by gel filtration and reversed-ph ase chromatography, and subjected to N-terminal sequencing. The IgE-binding ability of the purified proteins was studied by ELISA, and their in vivo r eactivity was studied by skin prick testing. Results: IgE antibodies from pooled patient sera were bound to 65-kd and 40 -kd wheat proteins in immunoblotting, The 65-kd allergen was a previously u ndescribed wheat protein, showing 61% sequence identity to gamma-gliadin, w hereas the 40-kd allergen had 100% identity to alpha-gliadin, In ELISA, all 18 patients showed elevated IgE levels to the novel gamma-like gliadin, an d 13 of the patients showed elevated IgE levels to the alpha-gliadin. None of the 54 control subjects with wheat allergy, urticaria, or coeliac diseas e had IgE antibodies to the gamma-like gliadin. The in vivo reactivity of t he gamma-like gliadin was verified by positive skin prick test responses in all of the 15 patients who were tested. During the follow-up on a gluten-f ree or wheat-free diet, 3 patients experienced reactions after having unkno wingly eaten wheat before exercise, but all the other : patients who were a dhering to the diet remained symptom-free. Conclusion: This study shows that wheat is a frequent cause of food-depende nt, exercise-induced anaphylaxis and suggests that the major allergen is a previously undescribed gamma-like gliadin. For screening of this life-threa tening allergy, me recommend skin prick testing with crude gliadin and we r ecommend a gluten-free diet for treatment.