Wheat sensitization : more than food allergy

Sammanfattning: Background: Wheat is one of the six most common foods responsible for food allergies in children and is introduced into the diet early in life. In children ingestion of wheat can lead to a variety of clinical manifestations, including cutaneous, gastrointestinal and respiratory symptoms. The methods commonly used in clinical practice to diagnose wheat allergy (WA) - medical history, skin prick test and IgE-antibodies (IgE-ab) to wheat are of limited value in diagnosing clinically relevant WA. One reason for this may be that wheat, since it is a grass from the Poaceae family, contains several allergenic proteins, many of which are known to cross-react with grass pollen allergens. An oral challenge test is recommended to confirm WA diagnosis. Since wheat is such a commonly used food, a food restriction can be complicated both for the affected individual as well as for the family. Aim: The aim of this thesis is to study the utility of different diagnostic methods to identify truly wheat allergic patients. Furthermore we wanted to compare the impact of WA and grass allergy on the quality of life (QoL) of children with diagnosis wheat or grass allergy and their parents’. Method: Sixty-three children diagnosed with wheat allergy (wheat group) and 72 grass allergic children (grass group) responded to a quality of life questionnaire and provided blood. The wheat group underwent an open wheat challenge where the children were eating increasing amounts of wheat under controlled conditions. IgE- ab against wheat, ω-5 gliadin, low molecular weight glutenin (LMW glutenin), high molecular weight (HMW glutenin) and the α-, β-, γ-, and ω-5 gliadin (gliadin) were analysed. Grass allergic children were analysed for seven grass-specific components (Phl p 1, Phl p 2, Phl p 4, Phl p 5, Phl p 6, Phl p 7, Phl p 11 and Phl p12), three wheat-specific allergen components (Tri a 14, Tri a 19 and gliadin), as well as cross-reacting carbohydrate determinants (CCD). Blood samples for CD-sens (basophil activation analysis) were taken for 24 individuals in wheat group. Inhibition test was used to analyse whether there is cross-reactivity between wheat and grass. This is done by to the patient's serum adding an extract of an allergen; antibodies bind to the allergen and then measure the residual activity. Results: Half of the wheat allergic individuals tolerated wheat at the challenge (non-WA). The IgE-ab level against ω-5-gliadin was significantly higher in the WA compared to the non-WA children. All children in the WA group had IgE-ab against ω-5 gliadin, low respectively high molecular weight glutenin and/or gliadin. We could also see a positive correlation between levels of IgE-ab against these components and the severity of the reaction. A majority of the grass allergic children had low levels of IgE-ab to wheat (median 0.52 kUA/L) and 87% had IgE-ab to birch. By inhibition we investigated whether cross-reactivity between grass pollen and wheat could be explained by two allergens commonly found in grass, profilin and CCD. These components could explain the cross-reactivity only in a third of cases. Both those with wheat and grass allergies were positive in the CD-sens, with stimulation of wheat and grass. There was a trend to higher CD-sens values to wheat in the WA group compared to the non-WA. Children in the wheat group had generally poorer quality of life than children in the grass group. The parents to the children in the wheat group experienced a significantly poorer quality of life compared with grass group. Children and parents in the grass group had a good agreement in the quality of life questionnaire but not for all domains in the wheat group. Conclusion: Based on the results of this thesis half of the children with a doctor´s diagnosed wheat allergy seem to avoid wheat unnecessarily. The reason for this may be that they developed tolerance over time or that the individual is falsely diagnosed due to cross-reactivity between wheat and grass pollen. We have shown that analysing IgE- ab against gliadins and glutenins increases the diagnostic accuracy for wheat allergy and distinguishes between those with wheat allergies from those with IgE-ab to wheat due to cross-reactivity with grass. CD-sens with wheat extract has a limited value -but may be useful when individual wheat proteins are used for stimulation. Quality of life was impaired in families with wheat-allergic children compared to families with grass-allergic individuals. This further strengthens the fact that the diagnosis of wheat allergy needs to be improved to avoid elimination diet and concerns about food allergy.