Original article IgE antibodies to x-5 gliadin associate with immediate symptoms on oral wheat challenge in Japanese children Food allergies account for 20% of acute urticaria, are present in 37% of children with moderate to severe atopic dermatitis and approximately 5% with atopic asthma and are the most frequent cause of anaphylaxis outside the hospital setting (1). Wheat is amongst the six foods responsible for approximately 90% of food allergies in children and is the third most common immediate type food allergens in Japanese children (2). The most common presentations of food allergy are cutaneous followed by multiorgan reactions. Wheat is less likely to cause multiple organ system reaction on challenge when compared with peanut, milk and egg in sensitized individuals (3). Wheat-specific immunoglobulin E (IgE) concentrations do not seem to be such useful predictors of the challenge test outcome enabling reduc- tion of these tests, in particular when compared with milk-, egg- and peanut-specific IgE concentrations (4). The frequently observed false-positive IgE reaction to wheat and other cereals in grass-pollen-allergic patients is explained by clinically insignificant cross-reactivity between the water/salt-soluble proteins (5). Therefore, identification of proteins associated with symptoms to wheat is of importance. Efforts have been made to identify new proteins that may be involved in food allergy to wheat (6–9). However, only a few of several wheat proteins recognized by the IgE of sensitized individuals have been characterized at the molecular level. Gliadins in particular have been implicated in IgE-mediated allergy to ingested wheat. They are seed storage proteins Background: Gliadins have been implicated in immunoglobulin E (IgE)-medi- ated allergy to ingested wheat and x-5-gliadin is known to represent a major allergen in wheat-dependent exercise-induced anaphylaxis. Less known is whether x-5-gliadin is a clinically relevant allergen in children with immediate allergy to ingested wheat. This study investigates whether specific IgE antibodies to x-5-gliadin (sIgE-x-5-gliadin-ab) could be used as a marker for oral wheat challenge outcome in wheat-sensitized children. A secondary objective was to study whether the level of sIgE-x-5-gliadin was related to symptom severity in children with a positive challenge test. Methods: Serum samples from 88 children sensitized to wheat, of whom 35 underwent wheat challenge, were collected consecutively. sIgE-x-5-gliadin-ab was related to a physicianÕs diagnosis of wheat allergy and challenge symptoms. Results: The mean concentration of sIgE-x-5-gliadin-ab was 7.25 kU A /l in patients with wheat allergy and 1.08 kU A /l in patients with no wheat allergy (P < 0.01). sIgE-x-5-gliadin-ab was only detected in 12 of the non-wheat allergic children and 11 of them had a specific IgE to wheat below 1.30 kU A /l. Children reacting with severe symptoms upon challenge (n = 8) had increased levels of sIgE-x-5-gliadin-ab compared to children with moderate, mild or no symptoms (P < 0.001). Conclusions: The presence of sIgE-x-5-gliadin-ab is related to the reaction level to wheat challenge outcome in wheat-sensitized children. The sIgE-x-5-gliadin- ab was found to be associated with a strong convincing history of wheat allergy also in those cases when oral food challenge was avoided. The sIgE-x-5-gliadin- ab level may serve as a marker for clinical reactivity in wheat-sensitized individuals. K. Ito 1 , M. Futamura 1 , M. P. Borres 2,3 , Y. Takaoka 1 , J. Dahlstrom 3 , T. Sakamoto 4 , A. Tanaka 5 , K. Kohno 6 , H. Matsuo 7 , E. Morita 6 1 Department of Allergy, Aichi ChildrenÕs Health and Medical Center, Obu, Japan; 2 Department of Pediatrics, Sahlgrenska Academy of Gçteborg University, Gothenburg, Sweden; 3 Medical Department, Phadia AB, Uppsala, Sweden; 4 Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan; 5 Scientific Affairs, Phadia KK, Tokyo, Japan; 6 Department of Dermatology, Shimane University School of Medicine, Izumo, Japan; 7 Division of Clinical Pharmacotherapeutics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan Key words: food challenge; x-5 gliadin; IgE; recombinant; wheat. Komei Ito Department of Allergy Aichi ChildrenÕs Health and Medical Center 1-2 Osakada Morioka Obu-city Aichi 474-8710 Japan Accepted for publication 18 March 2008 Abbreviations: IgE, immunoglobulin E; kU A /l, kilounits of allergen- specific IgE per litre; OFC, oral food challenge; DBPCFC, double- blinded placebo-controlled food challenge; SPT, skin prick test; WDEIA, wheat-dependent exercise-induced anaphylaxis; rx-5 gli- adin, recombinant x-5 gliadin; WA, child characterized with wheat allergy; NoWA, child without wheat allergy. Allergy 2008: 63: 1536–1542 Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard DOI: 10.1111/j.1398-9995.2008.01753.x 1536