Wheat allergy is one type of adverse immunologic reactions to wheat which can impair the quality of life and cause significant morbidity. Allergic reactions to wheat are essentially immunoglobulin E (IgE)-mediated. Although non-IgE-mediated reactions can contribute to wheat allergy, their mechanism is not well understood.
Typical manifestations of wheat allergy include the generation of allergen specific IgE antibodies and subsequent release of chemical mediators such as histamine, leukotrienes, and platelet factor.
Clinically identified types of wheat allergy
- Dietary and food allergy caused by ingestion of gluten-containing foods.
- Wheat-dependent exercise induced anaphylaxis (WEDIA) is induced by wheat. consumption prior to vigorous physical activity.
- Inhalation of gluten-containing flour commonly known as occupational baker‘s asthma.1
This discussion will focus only on wheat allergy caused by wheat ingestion.
Main distinctions between wheat allergy and celiac disease:
- Celiac disease is a lifelong condition while wheat allergy can be outgrown.
- Celiac disease is an autoimmune (different from immune) disease while wheat allergy is an immune-mediated condition.
- Celiac disease involves the gliadins and glutenins fractions of wheat proteins while wheat allergy can also be caused by the albumins and globulins fractions of wheat proteins.2
- Celiac disease immune response causes imminent harm to the small intestines; except in extreme cases such as anaphylaxis, wheat allergy response is often temporary.
Prevalence and risk factors
Approximately 0.4% of the world’s population are allergic to wheat, with most of the cases being children, who typically outgrow their allergy between the ages of 3 to 6 years.3
In the US, the prevalence of wheat-based food allergy is estimated at 0.2 to 1%.4 In Europe, 10–20% of food allergy sufferers are typically allergic to wheat. This allergy is most prevalent in Northern Europeans. In young children (≤ 3 years), wheat allergy ranged from 0.8 % in Sweden5 to 2.1 % in Finland.6 The lowest prevalence (0.2 %) of self-reported allergy to wheat was found in a group of 7–13-year-olds in Greece.7 For the same age category, the highest prevalence was reported in France at 1.5 %.8
It should be noted that for more accurate assessment of the prevalence of food allergies, it is important to distinguish between self-reported and clinician-diagnosed conditions.
The two main factors that can increase a person’s risk of developing wheat allergy are:9
- Family history: wheat and other food allergies in children seem to be inherited from their parents. The timing of initial exposure to cereal grains and family history may modify the risk of an allergy to wheat (Poole et al., 2006).10
- Age: Small children are more likely to develop wheat allergy compared to adults, presumably due to their immature immune and digestive systems. Most children outgrow wheat allergy although adults can develop the condition a result of cross-sensitivity to grass pollen.
Allergens involved in development
Both gluten and non-gluten proteins (mostly enzymes and enzyme inhibitors) have been identified as precipitating agents.
In wheat and Triticum aestivum, allergens from the profilin (Tri a12), prolamin (Tri a14, Tri a19, Tri a26, Tri a36) and alpha-purothionin (Tri a37) families have been implicated in wheat allergy.11 Typical primary sequences found in gliadins triggering this allergy are QQIPQQQ, PQQPFP, QQQFPGQQQQ and similar peptides from gliadin and glutenin.12,13
Non-gluten proteins such as α-amylase/trypsin inhibitor and lipid transfer proteins (LTP), cupins and profilins, important in B-cell epitopes have also been found to cause wheat allergy.14
Wheat allergy symptoms
Reactions to wheat consumption and the appearance of symptoms after food ingestion can be immediate or delayed. Immediate reactions can occur in 1-2 hours after wheat ingestion. Non-immediate reactions occur from several hours to 1 or 2 days after food intake, and are characterized by eczematous manifestations and loose stools or diarrhea.
Wheat allergy clinical manifestations can be very similar to those of celiac disease and other types of food allergy. Typical symptoms include:
- Skin, mouth, and throat (e.g., contact urticaria and contact dermatitis)
- Respiratory tract (allergic rhinitis and Baker’s asthma)
- The gastrointestinal tract (e.g., abdominal pain and diarrhea)
- Anaphylactic shocks (in rare cases)
How to diagnose wheat allergy
Diagnosis of wheat allergy, as well as other food allergies, relies on the observation of clinical signs, and their timing in response to food challenge. Clinicians often reported difficulties in diagnosing this allergy because of the possible confusion between pollen and the allergens and the difficult expression of the disease. This often leads to misdiagnosis and subsequent unsuccessful therapy or food avoidance.
Typical tools for diagnosis consist of:
- Food diary: is supervised by a health professional to track diet composition, time of consumption, symptoms, etc.
- Skin Prick Test (SPT): drops of a diluted allergen/food are placed on the patient’s arm or back followed by piercing the skin with a fine tip needle to introduce the allergen to the body. Itching, swelling, or redness is an indication of wheat allergy. A positive SPT is not a definite test and further confirmatory tests will be required.
- IgE assays: this is a blood test to detect antibodies for the allergen.
- Oral provocation tests: should be done in a hospital/clinic setting to ensure proper monitoring of symptoms. The patient will be offered small doses of the suspected allergen, followed by gradual increase in the dose over several hours or days.
A novel epidemiological analysis using molecular component-resolved diagnosis was introduced recently to correlate the interaction between allergen exposure gradient and patient sensitization.
Like other food allergies, treatment of wheat allergy is focused on avoidance of food containing heat and similar cereals. Depending on the severity of the condition, two types of treatments are available to allergy sufferers:
- A wheat-free diet is indicated as long-term therapy.
- Acute treatment includes application of epinephrine or antihistamines. Epinephrine or adrenaline can be used as an emergency measure in case of anaphylaxis to open airways and help restore breathing and to correct extreme low blood pressure that may ensue. Patients with severe wheat allergy should carry epinephrine doses all the time. Antihistamines function by lowering the patient’s immunity and should be taken under the supervision of a healthcare professional.
- Baker’s asthma, a unique class of wheat allergy can only be treated with immunotherapy.
Can food processing reduce wheat allergenicity?
Conflicting data are available on the impact of wheat and cereal processing, mainly heat processing, on wheat allergy.
- Baking, although can destroy the immunogenicity of wheat allergen, amylase inhibitor, prolamins are thermostable and thus their immunogenicity is not affected.15 Another study found that IgE-binding capacity remained unaltered in breadcrumbs and even increased in the crust, demonstrating the maintenance or the formation of new epitopes. Deamidation of gliadin was shown to reduce IgE-binding.16
- Proteolytic enzymatic treatments as well as microwave heating can decrease the immunoreactivity of wheat flour, but the negative impact on the dough rheological properties was detrimental, making it unsuitable for baking.17
- Fermenting wheat bread with Lactobacilli can significantly reduce its immunoreactivity by 20-60 %, depending on the antibody used for detection.18
- Baldo, B.A. and Wrigley, C.W. IgE antibodies to wheat flour components. Studies with sera from subjects with baker’s asthma or coeliac condition. Clin. Allergy, 1978, 8(2), pp: 109-1024. DOI: 10.1111/j.1365-2222.1978.tb00456.x
- Wieser, H., Koehler, P. and Scherf, K.A. (Eds). Wheat-An Exceptional Crop. Botanical Features, Chemistry, Utilization, Nutritional and Health aspects, 2020, Woodhead Publishing and AACC International Press; 1st edition, pp, 300.
- Biesiekierski, J.R., Newnham, E.D., Irving, P.M., Barrett, J.S., Haines, M., Doecke, J.D., Shepherd, S.J., Muir, J.G., and Gibson, P.R., Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial., Am. J. Gastroenterol., 2017, 106: 508-514.
- Cianferoni, A. Wheat allergy: Diagnosis and management. J. asthma Allergy, 2016, 9, pp: 13-25; PubMed: 26889090.
- Ostblom, E., Lilja, G., Pershagen, G., van Hage, M. and Wickman, M. Phenotypes of food hypersensitivity and development of allergic diseases during the first 8 years of life. Clin. Exp. Allergy, 2008, 38, pp. 1325-1332.
- Pyrhonen, K., Nayha, S., Kaila, M., Hiltunen, L. and Laara, E. Occurrence of parent-reported food hypersensitivities and food allergies among children aged 1-4 yr. Pediatr. Allergy Immunol., 2009, 20, pp: 328-338.
- Zannikos, K., Sakellariou, A., Emmanouil, E., Tzannis, K., Michopoulou, C., Sinaniotis, A., Xepapadaki, P., Saxoni-Papegeorgiou, P., and Papadopoulus, N. The prevalence of parentally perceived food hypersensitivity in Greek schoolchildren. Allergy (Special Issue): Abstracts of the XXVII EAACI Congress of the Europ. Acad. Allerg. and Clin. Immunol., Barcelona, Spain, June 7-11, 2008, 63, s88, p: 318.
- Touraine, F., ouzeau, J., Boullaud, C., Dalmay, F., and Bonnaud, F. Survey on the prevalence of food allergy in school children. Rev. Franc. Allergy Immunol. Clin., 2002, 42, pp: 763-768.
- Wheat allergy. https://www.mayoclinic.org/diseases-conditions/wheat-allergy/symptoms-causes/syc-20378897.
- Poole, J.A., Barriga, Leung, D.Y., Hoffman, M., Eisenbarth, G.S., Rewers, M. and Norris, J.M. Timing of initial exposure to cereal grains and the risk of wheat allergy. Pediatrics, 2006, 117, pp: 2175-2182.
- Radauer, C., Nandy, A., Ferreira, F., Goodman, R.E., Larsen, J.N., Lidholm, J., Pomes, A., raulf-Heismoth, M., Rozynek, P., Thomas, W.R. and Breiteneder, H. Update of the WHO/IUIS allergen nomenclature database based on analysis of allergen sequences. Allergy, 2014, 69 (4), pp: 413-419.
- Matsuo, H., Morita, E., Tatahm, A.S., Morimoto, K., Horikawa, T., Osuan, H., Ikezawa, Z., Kaneko, S., Kohno, K. and Dekio, S. Identification of the IgE-binding epitope in omega-5 gliadin, a major allergen in wheat-dependent exercise-induced anaphylaxis, J. Biol. Chem., 2004, 279, pp: 12135-12140.
- Denery-Papini, S., Bodinier, M., pineau, F., Triballeau, S., tranquet, O., Adel-Patient, K., Moneret-vautrin, D.A., Bakan, B., Marion, D., Mothes, D., Mameri, H., and Kasarda, D. Immunoglobulin-e-binding epitopes of wheat allergens in patients with food allergy to wheat and in mice experimentally sensitized to wheat proteins. Clin. Exp. Allergy, 2011, 41, pp: 1478-1492.
- Sander, I., Rozynek, P., rihs, H.P., van Kampen, V., Chew, F.T., Lee, W.S., Kotschy-Lang, N., Merget, R., bruning, T. and Raulf-Heimsoth, M. Multiple wheat flour allergens and cross-reactive carbohydrate determinants bing IgE in baker’s asthma. Allergy, 2011, 66, pp: 1208-1215.
- Simonato, B., Pasini, G., Ginnattasio, M., Peruffo, A.D., De Lazzari, F. and Curioni, A. Food allergy to wheat products: the effect of bread baking and in vitro digestion on wheat allergenic proteins. A study with bread dough, crumb, and crust, J. Agric. Food Chem., 2001, 49, pp: 5668-5673.
- Kumagi, H., Suda, A., Sakuri, H., Kumagai, H., arai, S., inomata, N. and Ikezawa, Z. improvement of digestibility, reduction in allergenicity, and induction of oral tolerance of wheat gliadin by deamidation, Biosci., Biotechnol. Biochem., 2007, 71, pp: 977-985.
- Susanna, S. and Prabhasankar, P. A comparative study of different bioprocessing methods for reduction in wheat flour allergens. Eur. Food Res. Technol., 2011, 233, pp: 999-1006.
- Leszcznska, J., Diowksz, A., Lacka, A., and Wolska, K. Evaluation of immunoreactivity of wheat bread made from fermented wheat flour. Czech. J. food Sci., 2012, 30, pp: 336-342.