Identification of gibberellin‐regulated protein as a new allergen in orange allergy

Background To date, three orange allergens have been reported. However, it is still unclear whether gibberellin‐regulated proteins (GRPs), identified as new allergens in other fruit allergies, are also involved in orange allergy. Objective To investigate the allergenicity of orange GRP and to determine the clinical characteristics of patients with orange allergy who are sensitized to orange GRP. Methods We enrolled 14 patients (four men, 10 women, mean age: 29.6 years) who were diagnosed with orange allergy based on relevant clinical history, positive skin test, and/or positive challenge test. Orange GRP (molecular weight: 6941.6 Da) was purified by ion‐exchange column chromatography. To test for orange GRP‐specific IgE, we performed ELISA, basophil activation tests, and skin prick tests. Cross‐reactivity of orange GRP with native peach allergen nPru p 7 and Japanese apricot nPru m 7 was analysed by ELISA inhibition assays. IgE specific for orange, grapefruit, and peach allergens rPru p 1, rPru p 3, and rPru p 4 was measured using ImmunoCAP. Results Twelve of the 14 patients (85.7%) were positive for orange GRP allergy in at least one test: 71.4% (10/14) were positive by ELISA, 50% (3/6) were positive in the basophil activation test, and 100% (4/4) were positive in the skin prick test. ELISA inhibition assays revealed cross‐reactivity of orange GRP with both nPru p 7 and nPru m 7. The patients showed variable positivity for specific IgE against orange, grapefruit, rPru p 1, rPru p 3, and rPru p 4 (57.1%, 71.4%, 7.1%, 0%, and 21.4%, respectively). The most frequent symptoms of orange GRP allergy were facial swelling and oropharyngeal symptoms. Conclusions and Clinical Relevance Orange GRP may be involved in orange allergy and may be a cross‐reactive allergen between citrus fruits and the Rosaceae family of fruits.