Rye γ‐70 and γ‐35 secalins and barley γ‐3 hordein cross‐react with ω‐5 gliadin, a major allergen in wheat‐dependent, exercise‐induced anaphylaxis

Abstract

Patients with wheat-dependent, exercise-induced anaphylaxis experience severe allergic reactions when exercising after ingestion of wheat. The major wheat allergen associated with these reactions is a omega-5 gliadin, and patients following a gluten-free diet have remained free of symptoms. The aim of this study was to examine whether allergens cross-reacting with wheat omega-5 gliadin are present in rye, barley and oats. Sera from 23 adult patients with wheat-dependent, exercise-induced anaphylaxis were examined. Cereal allergens cross-reacting with wheat omega-5 gliadin were identified by immunoblot inhibition. The cross-reactive allergens were purified by gel filtration and reversed-phase chromatography and submitted to amino acid sequencing. Cross-reactivity was further studied by IgE ELISA and ELISA inhibition, and in vivo reactivity by skin prick testing. In immunoblotting rabbit anti-omega-5 gliadin antibodies bound to 70 kDa and 32 kDa proteins in rye and a 34-kDa protein in barley, but not to proteins in oats. N-terminal sequencing identified these proteins as rye gamma-70 secalin, rye gamma- 35 secalin and barley gamma-3 hordein, correspondingly. In ELISA 21/23 (91%) patients with wheat-dependent, exercise-induced anaphylaxis showed IgE antibodies to purified gamma-70 secalin, 19/23 (83%) to gamma-35 secalin and 21/23 (91%) to gamma-3 hordein. In ELISA inhibition omega-5 gliadin inhibited over 90% of the IgE binding of pooled patient sera to solid-phase gamma-secalins and gamma-3 hordein. Skin prick testing gave positive reactions to gamma-70 secalin in 10/15 (67%) patients, to gamma-35 secalin in 3/15 (20%) patients and to gamma-3 hordein in 7/15 (47%) patients. The results of this study show that gamma-70 and gamma-35 secalins in rye and gamma-3 hordein in barley cross-react with omega-5 gliadin, a major allergen in wheat-dependent, exercise-induced anaphylaxis. These findings suggest that also rye and barley may elicit symptoms in patients with wheat-dependent, exercise-induced anaphylaxis.

Study of IgE Antigenic Relationships in Hypersensitivity to Hydrolyzed Wheat Proteins and Wheat-Dependent Exercise-Induced Anaphylaxis

“…As already observed [15], IgE from the WDEIA patient reacted essentially only with γ-3 among total hordeins, and with γ-35 and γ-75 secalins among total rye prolamins (fig. 4a).…”

“…Its sequence has been published very recently, after the completion of this work [14]. Moreover, at the IgE level, antigenic relationships were demonstrated between ω-5 gliadin and barley γ-3 hordein and two rye γ-35 and γ-75 secalins [15]. Fast ω gliadins, which correspond to ω-5 gliadins, have also been suspected to be allergenic in bakers’ asthma [9].…”

Common food allergens and their IgE-binding epitopes

“…106 Water/salt-insoluble wheat allergens Gliadins and glutenins are water/salt-insoluble wheat proteins that have been identified as causative allergens in patients with wheat food allergy, baker's asthma, and WDEIA. 10,35,107,113,117 u5-Gliadin (Tri a 19) is a major allergen in WDEIA 138,139 and children with immediate allergy to ingested wheat. 140 Because of the presence of a repetitive domain, there are many IgE epitope sequences in u5-gliadin; however, the consensus sequence comprising QQX 1 PX 2 QQ (X 1 ¼ L, F, S, I; X 2 ¼ Q, E, G) has been identified as the IgE-binding epitope in Japanese and European patients.…”

Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes

“…As to the cross-reactivity among different cereal grains, cross-reaction between a 65 kDa gliadin, a 70 kDa secalin from rye and a γ-3-hordein from barley was demonstrated in WDEIA (Palosuo et al, 2001a). Although food allergy to cereals is often due to monosensitisation (Jones et al, 1995), 20 % of patients with cereal allergy demonstrate clinical reactivity (DBPCFC) to more than one cereal grain.…”