A case of food-dependent exercise-induced anaphylaxis due to grape gibberellin-regulated protein.

To the Editor, Increasing incidences of anaphylaxis caused by fruits have recently been reported.1 Reports on peaches and apples causing immediate hypersensitive reactions and fooddependent exerciseinduced anaphylaxis (FDEIA) are noted; however, reports on grapes are limited.2,3 While gibberellinregulated protein (GRP) has been identified as an allergen that induces severe allergic reactions in some fruits and is present in grapes,4 its involvement in grape allergy is unknown. Here, we report a case of FDEIA due to grapes with positive results in the skin prick test (SPT) and enzymelinked immunosorbent assay (ELISA) with purified grape GRP, and demonstrated the crossantigenicity of grape and peach GRPs. To the best of our knowledge, this is the first report of FDEIA caused by grape GRP. An 11yearold boy presented with abdominal pain, respiratory distress, and systemic urticaria after eating grapes, followed by playing soccer for 30 min, was brought to our emergency room and admitted after an intramuscular adrenaline injection. He had a history of atopic dermatitis, allergic rhinitis, and peach allergy since the age of 9 years when he developed systemic urticaria after ingesting one raw peach. According to the Japanese Guidelines for Food Allergy, an oral food challenge (OFC) was performed where 600 g of grapes was negative. On another day, the exercise provocation test (treadmill test, the standard Bruce protocol) was negative for intake of 300 g of grapes and exercise for 15 min. On yet another day, the exercise provocation test was conducted again with the combination of 10 mg/kg (0.28 g) acetylsalicylic acid followed by 350 g of grapes 30 min later and 15 min of exercise 30 min after that. Eye redness, pruritus at the tips of the extremities, and a rash over the entire face appeared within 2 min. After 5 min, he had facial edema and developed respiratory distress (Figure S1). Adrenaline was administered intramuscularly in the left vastus lateralis, and his symptoms improved notably. Thus, he was diagnosed with FDEIA secondary to grapes. He was discharged after treatment and counseling, and had no recurrences thereafter. His specific immunoglobulin E (sIgE) titers were measured using ImmunoCAP® (Thermo Fisher Diagnostics, Inc.). The sIgE titers were positive for rPru p 7 (4.24 UA/ml), peach (1.5 UA/ml), apple (0.79 UA/ml), cedar (41.2 UA/ml), and cypress (19.2 UA/ml). It was positive for alder (5.55 UA/ml) but negative for rPru p 1, 3, and 4 (<0.10 UA/ml). These results strongly suggested the involvement of GRP, which was proven by introducing purified grape GRP. This study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Institutional Review Board of Fujita Health University (approval number: HM21417). Written informed consent was obtained from the patient's parents for this study. Detailed information on the materials and methods used is provided in the online supplement. Grape and peach GRPs were purified using monoclonal antibodies obtained against peach GRP.5 On sodium dodecyl sulfate– polyacrylamide gel electrophoresis (SDSPAGE), grape GRP showed a band that was consistent with its expected size (Figure S2A) and was confirmed by mass spectrometric analysis (51.1% sequence coverage) (Figure S2B). The SPT revealed positive reactions of the patient to both purified peach and grape GRPs, and negative reactions to lipid transfer protein (LTP), pathogenesisrelated class 10 (PR10) proteins, and profilin (Table 1). LTP was reported to be the causative antigen