Background: Wheat allergy is the third most common food allergy that develops during infancy in Japan. To identify factors associated with persistent wheat allergy, we assessed the rate of tolerance acquisition among Japanese children aged less than 6 years with an immediate-type wheat allergy using the oral food challenge (OFC) method. Methods: This retrospective cohort study included 83 children (born in 2005–2006) who had a history of immediate-type allergic reaction to wheat and were followed until 6 years of age. The subjects were divided to form “tolerant” (n = 55; tolerance acquired by 6 years of age) and “allergic” (n = 28; tolerance not acquired by 6 years of age) groups based on their OFC results. Results: The rates of tolerance acquisition to 200 g of udon noodles at 3, 5, and 6 years of age were 20.5% (17/83), 54.2% (45/83), and 66.3% (55/83), respectively. The total number of anaphylactic reactions experienced prior to 3 years of age in response to all foods (p < 0.01) and to wheat (p = 0.043) was significantly higher in the allergic than in the tolerant group. Wheat- and ω-5 gliadin-specific immunoglobulin E (IgE) levels were significantly higher in the allergic group than in the tolerant group (p < 0.01), and wheat-specific IgE levels were more likely to increase after infancy in the allergic group. Conclusions: A history of anaphylaxis to all foods including wheat and/or a high level of wheat- or ω-5 gliadin-specific IgE antibodies were identified as risk factors for persistent wheat allergy.

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