Omega-5 Gliadin Research Articles

Wheat-Dependent Cofactor-Augmented Anaphylaxis: A Prospective Study of Exercise, Aspirin, and Alcohol Efficacy as Cofactors

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe and potentially life-threatening allergy caused by wheat ingestion and most commonly in combination with exercise. To investigate the role and impact of different cofactors (exercise, aspirin, and alcohol) in patients with WDEIA. We studied 25 adult patients with WDEIA. Diagnostic workup included specific IgE to omega-5 gliadin and skin prick test with wheat flour and gluten. Titrated oral challenge was performed with gluten at rest, combined with treadmill exercise, aspirin, alcohol, or a combination of exercise and aspirin. A positive challenge to gluten was found at rest (without cofactors) in 48% (12 of 25), with exercise in 92% (23 of 25), with aspirin in 84% (21 of 25), with alcohol in 56% (9 of 19), and with a combination of exercise and aspirin in 82% (18 of 22) of the patients. With exercise as a cofactor, the median threshold was 24 g (range, 4.8-80 g), with aspirin 8 g (range, 2.4-80 g), and with alcohol 28 g (range, 0-45 g). The combination of 2 cofactors (exercise and aspirin) resulted in a median threshold of 4.3 g (range, 1.1-48 g). The threshold for the clinical reaction was lowered by 63%, 83%, 36%, and 87%, respectively, compared with at rest. The mean severity grade (scale 0-5) according to the Sampson severity score at rest was 0.8 (range, 0-2), and when combined with exercise 2.1 (range, 0-5), with aspirin 1.9 (range, 0-5), with alcohol 0.8 (range, 0-2), and with the combination of exercise and aspirin 1.5 (range, 0-2). Our results demonstrate that exercise and aspirin augment clinical reactions in WDEIA by lowering the threshold and increase the severity of the allergic reaction, whereas alcohol gives ambiguous results. Furthermore, a combination of 2 cofactors (exercise and aspirin) increases therisk of reactions.

How to diagnose food allergy.

To assess the recent studies that focus on specific immunoglobulin E (sIgE) testing and basophil activation test (BAT) for diagnosing IgE-mediated food allergies. The sIgE to allergen extract or component can predict reactivity to food. The cutoff value based on the positive predictive value (PPV) of sIgE can be considered whenever deciding whether oral food challenge (OFC) is required to diagnose hen's egg, cow's milk, wheat, peanut, and cashew nut allergy. However, PPV varies depending on the patients' background, OFC methodology, challenge foods, and assay methodology. Component-resolved diagnostics (CRD) has been used for food allergy diagnosis. Ovomucoid and omega-5 gliadin are good diagnostic markers for heated egg and wheat allergy. More recently, CRD of peanut, tree nuts, and seed have been investigated. Ara h 2 showed the best diagnostic accuracy for peanut allergy; other storage proteins, such as Jug r 1 for walnut, Ana o 3 for cashew nut, Ses i 1 for sesame, and Fag e 3 for buckwheat, are also better markers than allergen extracts. Some studies suggested that BAT has superior specificity than skin prick test and sIgE testing. The sIgE testing and BAT can improve diagnostic accuracy. CRD provides additional information that can help determine whether OFCs should be performed to diagnose food allergy.

A Multicenter Evaluation of Diagnosis and Management of Omega-5 Gliadin Allergy (Also Known as Wheat-Dependent Exercise-Induced Anaphylaxis) in 132 Adults

Omega-5 gliadin allergy (also known as wheat-dependent exercise-induced anaphylaxis) is a rare allergy to wheat that often presents with intermittent severe anaphylaxis in the context of a cofactor, such as exercise. To undertake a detailed clinical characterization of the largest cohort of patients with omega-5 gliadin allergy to date. We retrospectively analyzed the demographic characteristics, presentation, investigation, and management of 132 patients presenting with omega-5 gliadin allergy in 4 UK centers. There were significant delays in diagnosis of 1 to 5 years (40% of patients) and more than 5 years (29% of patients). The commonest cofactors were exercise (80%), alcohol (25%), and nonsteroidal anti-inflammatory drugs (9%). A minority of patients (11%) had no identifiable cofactor. The level of specific IgE to omega-5 gliadin does not predict the severity of allergic reactions. Patients who adhered to a gluten-free diet and those who avoided wheat in combination with exercise achieved the largest reductions in subsequent allergic reactions of 67% and 69%, respectively. Omega-5 gliadin allergy is a rare wheat allergy that presents with severe anaphylaxis. The diagnosis is frequently delayed, and therefore we recommend that all adult patients presenting with anaphylaxis of unclear cause should have omega-5 gliadin specific IgE tested. A gluten-free diet or avoidance of wheat-based meals in combination with exercise (if the cofactor is exercise) helps to significantly decrease the risk of future allergic reactions. However, antihistamines and an epinephrine autoinjector must always be prescribed because one-third of patients continue to have allergic reactions despite dietary advice.

Exercise Lowers Threshold and Increases Severity, but Wheat-Dependent, Exercise-Induced Anaphylaxis Can Be Elicited at Rest

Wheat-dependent, exercise-induced anaphylaxis (WDEIA) is a severe form of allergy in which exercise is being considered as mandatory. The diagnosis is often complex and the clinical reproducibility low. The aims of this study were to establish a standardized challenge method for the diagnosis of WDEIA and to investigate whether exercise is an essential trigger factor or alternatively an augmentation factor able to lower threshold and increase severity. We investigated 71 patients (age, 18.6-73.7 years) with a case history of WDEIA. Skin prick test (SPT) and measurement of specific IgE (sIgE) were followed by an oral food challenge with gluten at rest and in combination with treadmill exercise. A clinical reaction was elicited in 47 of 71 (66%), and in 26 of these (37%) the reaction could be elicited at rest. The median dose required at rest was 48 g (8-80 g) and in combination with exercise 24 g (4-80 g). Severity was significantly higher with exercise (2.3) than at rest (1.1) using Sampson severity score. In the challenge, SPT was positive to wheat in 93.6% (44 of 47) and to gluten in 95.7% (45 of 47). sIgE to wheat, gliadin, and omega-5 gliadin was present in 78.7% (37 of 47), 76.5% (36 of 47), and 91.4% (43 of 47) of the patients. Receiver operating characteristic-curve analysis for sIgE to omega-5 gliadin, a component of the gluten fraction and the major allergen in WDEIA, showed best sensitivity (91%) and specificity (92%) when gluten was combined with exercise. A challenge test with gluten at rest and combined exercise is a safe confirmatory test for WDEIA. A reaction can be elicited at rest (without exercise), but exercise is able to lower the threshold and increase the severity.

Gluten sensitivities and the allergist: Threshing the grain from the husks.

"Gluten sensitivity" has become commonplace among the public. Wheat allergy (WA) and celiac disease (CD) are well-defined entities, but are becoming a fraction of individuals following a gluten-free diet (GFD). Wheat allergy has a prevalence of <0.5%. Wheat, specifically its omega-5 gliadin fraction, is the most common allergen implicated in food-dependent, exercise-induced anaphylaxis. CD is a non-IgE hypersensitivity to certain cereal proteins: gluten in wheat, secalin in rye, hordein in barley, and to a lesser extent avenin in oat. It is a rare disease, with an estimated prevalence that varied widely geographically, being higher in Northern Europe and the African Saharawi region than in South-East Asia. In addition to suggestive symptoms, serologic testing has high diagnostic reliability and biopsy is a confirmatory procedure. Patients with CD have extra-intestinal autoimmune comorbid conditions more frequently than expected. A third entity is nonceliac gluten sensitivity, which has been created because of the increasing number of subjects who claim a better quality of life or improvement of their variety of symptoms on switching to a GFD. The phenomenon is being fueled by the media and exploited by the industry. The lack of a specific objective test has been raising substantial controversy about this entity. Allergists and gastroenterologists need to pay attention to the multitudes of individuals who elect to follow a GFD. Many such subjects might have WA, CD, or another illness. Providing them with appropriate evaluation and specific management would be of great advantages, medically and economically.

Allelic Analysis of Omega-5 Gliadin (Gli-B1) in Korean Wheat Cultivars

You-Ran Jang1†, Hye-Rang Beom1†, Jung-Bong Kim1, Chul-Soo Park2, Yeong-Tae Kim3, Chon-Sik Kang1,Sun-Hyung Lim1, Young-Mi Kim1, and Jong-Yeol Lee1*. Korean J. Breed. Sci. 2016;48:159-67. https://doi.org/10.9787/KJBS.2016.48.2.159

The clinical spectrum of omega-5-gliadin allergy.

IgE-mediated allergy to the wheat protein omega-5-gliadin (O5G) is associated with wheat-dependent exercise-induced anaphylaxis (WDEIA), where exercise acts as a cofactor, triggering anaphylaxis after wheat ingestion. The wider application of O5G-specific IgE (sIgE) testing has revealed that the manifestations of O5G allergy extend beyond WDEIA. This study documents clinical manifestations in a large series of patients with sIgE to O5G. A retrospective clinical audit was performed on adult patients with a positive O5G sIgE (>0.35kU/L) between 2007 and 2013 compared with a group who had negative O5G sIgE. Clinical characteristics and skin prick test (SPT) results were examined. Sixty-seven patients were characterised, 26 of whom presented with food-dependent exercise-induced allergy, whilst others presented with exercise-induced symptoms without apparent food association (16/67), idiopathic anaphylaxis (10/67), food-induced allergic symptoms without exercise (10/67) or recurrent acute urticaria (5/67). Specific IgE to O5G had 91% sensitivity and 92% specificity for wheat-related allergic symptoms. SPT had sensitivity of 92% and specificity of 84%. WDEIA is the most common manifestation of O5G allergy, but patients may present with a variety of allergic manifestations, and wheat allergy is not always obvious on history. Non-exercise cofactors or a lack of cofactors were identified in many patients. A distinctive feature of this allergy is that despite regular wheat ingestion, allergic reactions to wheat occur infrequently. Testing for sIgE to O5G should be considered in patients presenting with exercise-induced urticaria/anaphylaxis, idiopathic anaphylaxis and recurrent acute (but not chronic) urticaria.

Clinical and laboratory features, and quality of life assessment in wheat dependent exercise-induced anaphylaxis patients from central China.

Wheat dependent exercise-induced anaphylaxis (WDEIA) is a rare but potentially severe food allergy caused by the combination of wheat ingestion and physical exercise. The impact of WDEIA on quality of life (QOL) is unclear. This study characterized the clinical and laboratory features and investigated the QOL in WDEIA patients from Central China. Twenty-eight WDEIA patients were analyzed, and QOL was measured by validated Chinese version Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) and Food Allergy Independent Measure (FAIM) after obtaining the diagnosis. The results showed that half of the patients were females. The median onset age was 37 years old. The symptoms occurred within 1 h after wheat ingestion (26/28). Symptoms of anaphylaxis included cutaneous (26/28), respiratory (11/28), gastro-intestinal (5/28) and cardiovascular manifestations (27/28). Skin prick tests were positive to salt soluble (89.3%) and salt insoluble wheat allergen extracts (100%). Positive rate to wheat, gluten and omega-5 gliadin specific IgE was 64.3%, 92.9% and 92.9% respectively. Specific IgE to omega-5 gliadin with a cut-off value 0.83 KU/L offered highly efficient diagnostic criterion for WDEIA (sensitivity: 89.3%; and specificity: 88.9%). The mean scores of FAQLQ-AF and FAIM were 4.70 and 4.98 respectively and level of anti-omega-5 gliadin IgE had positive correlations with FAQLQ scores. Thereby, WDEIA is commonly found in mid-age adults. In most cases, multi-organs especially skin and cardiovascular systems are involved. Salt insoluble wheat allergen skin test and serum specific IgE to gluten and omega-5 gliadin help to diagnose WDEIA. QOL in WDEIA patients is severely impaired.

Diagnostic and Therapeutic Approach in Patients with Exercise-Induced Anaphylaxis

The prevalence of exercise-induced anaphylaxis is estimated to be about 2.36-5 % of all cases of anaphylaxis. The clinical manifestations of exercise-induced anaphylaxis include flushing, increase warmth, diffuse pruritus, urticaria, angioedema, bronchospasm, gastrointestinal symptoms, hypotension, and laryngeal edema. The main differential diagnosis is with cholinergic urticaria. Exercise-induced anaphylaxis may display food-dependence, with or without specific IgE sensitivity. The most commonly implicated foods are wheat (omega-5 gliadin), shellfish (especially shrimps), celery, corn, cow’s milk, mite-contaminated wheat flour, and peanuts. Interestingly, in these patients aerobic exercises alone, as well as the sole ingestion of the allergenic foods without associated exercises, do not cause anaphylaxis. The synergistic effect of both inducing factors is necessary for the occurrence of the anaphylactic manifestations. There may be drug-dependence in exercise-induced anaphylaxis. Implicated drugs and chemicals include NSAIDS, aspirin, antibiotics (cephalosporins), and the so-called anti-catabolic energizer supplements, such as beta-hydroxymethylbutyrate. Avoidance of eating the triggering foods is recommended when possible, and in temperate areas of the planet an additional preventive measure is not to exercise when there is high environmental exposure to pollens (then exercising indoors). It is also advisable to avoid exercising in extreme weather conditions (too hot, cold, or humid environments). Monoclonal anti-IgE (omalizumab) as a mast cell stabilizer with downregulation of the high affinity IgE receptors (FceRI) can have a potential role preventing these anaphylactic episodes.

Identification of wheat sensitization using an in-house wheat extract in Coca-10% alcohol solution in children with wheat anaphylaxis.

Identification of wheat sensitization by a skin prick test (SPT) is essential for children with wheat-induced anaphylaxis, since oral food challenge can cause serious adverse effects. Wheat allergens are both water/salt and alcohol soluble. The preparation of wheat extract for SPT containing both water/salt and alcohol soluble allergen is needed. To determine if a wheat extract using Coca's solution containing 10% alcohol (Coca-10% EtOH), prepared in-house, contians both water/salt and alcohol soluble allergens. Serum of children with a history of anaphylaxis after wheat ingestion was used. Wheat flour was extracted in Coca-10% alcohol solution. An SPT with both commercial and in-house wheat extracts was performed as well as specific IgE (sIgE) for wheat and omega-5 gliadin. Direct and IgE inhibition immunoblots were performed to determine serum sIgE levels against water/salt as well as alcohol soluble (gliadins and glutenins) allergens in the extracts. Six children with history of wheat anaphylaxis had positive SPT to both commercial and in-house extracts. They also had different levels of sIgE against wheat and omega-5 gliadin allergens. The results of direct immunoblotting showed all tested sera had sIgE bound to ~35 kDa wheat protein. Further IgE inhibition immunoblotting identified the ~35 kDa wheat protein as gliadin but not gluten allergen. The in-house prepared Coca-10% EtOH solution could extract both water/salt and alcohol soluble allergens. The ~35 kDa gliadin appears to be a major wheat allergen among tested individuals.

A review of biomarkers for predicting clinical reactivity to foods with a focus on specific immunoglobulin E antibodies.

The purpose of this study is to assess the latest studies that focus on specific immunoglobulin (Ig)E antibodies for predicting clinical reactivity to foods. Persistent hen's egg and cow's milk allergy patients have higher antigen-specific IgE levels at all ages than those who have outgrown these allergies. Recent studies on the natural histories of hen's egg and cow's milk allergies suggested that baseline antigen-specific IgEs are the most important predictors of tolerance. Oral immunotherapy (OIT), which is a novel therapeutic approach for food allergy, requires biomarkers for predicting outcomes after therapy. Several studies indicate that the initial antigen-specific IgE level may be a useful biomarker for the prognosis of OIT. Recently, component-resolved diagnostics (CRD) has been used for food allergy diagnosis. Current studies have suggested that Ara h 2, omega-5 gliadin and ovomucoid are good diagnostic markers for peanut, wheat and egg allergies, respectively. Antigen-specific IgE can be a useful biomarker for predicting clinical reactivity to food allergies. Monitoring hen's egg and cow's milk-specific IgE is useful for predicting prognosis, and baseline specific IgE levels may be associated with the outcome of OIT. The use of CRD provides us with a better tool for diagnosing food allergy.

Quantitative proteomic analysis of wheat grain proteins reveals differential effects of silencing of omega-5 gliadin genes in transgenic lines

Novel wheat lines with altered flour compositions can be used to decipher the roles of specific gluten proteins in flour quality. Grain proteins from transgenic wheat lines in which genes encoding the omega-5 gliadins were silenced by RNA interference (RNAi) were analyzed by quantitative 2-dimensional gel electrophoresis (2-DE). The precise effects of the genetic modifications on the proteome were assessed in four homozygous lines generated with the same RNAi construct. Two of the lines showed >80% decreases in omega-5 gliadins with only small changes in the levels of other gluten proteins. In the other two lines, omega-5 gliadins were not detectable by 2-DE. However, there were notable reductions in all omega-1,2 gliadins. Small decreases in several other gluten proteins were also detected in one of the lines. The other line showed notable decreases in three HMW-GS and an s-type LMW-GS, increases in two m-type LMW-GS and several alpha gliadins, as well as increases in both serpins and triticin. The study demonstrates that the same RNAi construct can have differential effects on the wheat grain proteome and highlights the importance of detailed proteomic analyses of transgenic grain prior to selecting lines for further assessment of flour quality and allergenic potential.

Quantitative evaluation of the symptoms provoked during the oral food challenge using the Anaphylaxis Scoring Aichi (ASCA)

The total scores ≥100 points were recorded in five egg white, two milk and four wheat challenges. The distribution of the total scores was not different among the target foods, and in total, 44.9% had at otal score≤10 points, 46.9% were between 11 to 40 points, and 8.1% were ≥41 points. A significant correlation coefficient was detected between the TS/Pro and sIgE for egg white (r=0.24, p<0.001), ovomucoid (r=0.28, p<0.001), milk (r=0.23, p<0.001), wheat (r=0.36, p<0.001), and omega-5 gliadin (r=0.41, p<0.001). Conclusion

The Sensitivity and Clinical Course of Patients with Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized to Hydrolyzed Wheat Protein in Facial Soap - Secondary Publication

Recently, an increasing number of patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) have been reported in Japan. Most of them had developed this condition during or after using hydrolyzed wheat protein (HWP)-containing soap (HWP-WDEIA). To clarify the relation between WDEIA and HWP-containing soap and their prognosis, we retrospectively studied the patients who visited Hiroshima University Hospital and were diagnosed as WDEIA from January 2010 to June 2011. We took detailed clinical histories, performed skin prick tests, serum immunoassays for antigen-specific IgE and basophil histamine release test, and followed up their clinical courses after the diagnosis. Among 36 patients with WDEIA, 30 patients had used only one type of HWP-soap. The patients with HWP-WDEIA were mainly women and had developed facial symptoms and angioedema. They suffered from blood pressure reductions less frequently than patients with conventional WDEIA. The levels of gluten-specific IgE were higher than those of omega-5 gliadin in patients with HWP-WDEIA (P < 0.05, One-way ANOVA). All patients with HWP-WDEIA were positive against HWP in histamine release test. Among the conventional wheat antigens, glutenins induced the highest histamine release from basophils of patients with HWP-WDEIA. The sensitivities of patients against glutens and glutenins were reduced over months along with the discontinuance of HWP-soap. The development of HWP-WDEIA is associated with the use of HWP-soap. The sensitivity to HWP that cross reacts with non-processed wheat may be reduced or possibly cured after the discontinuation of HWP-soap.

Wheat-dependent exercise-induced anaphylaxis in elderly patients

Food-dependent exercise-induced-anaphylaxis (FDEIA) is caused by aerobic exercise within 2 to 4 hours after ingestion of food. However, this clinical presentation can be variable in severity, and with respect to the quantity of food ingested and the exercise intensity. 1 Wong G.K.Y. Huissoon A.P. Goddard S. Collins D.M. Krishna M.T. Wheat dependent exercise induced anaphylaxis: is this an appropriate terminology?. J Clin Pathol. 2010; 63: 814-817 Crossref PubMed Scopus (32) Google Scholar , 2 Yacoub M.R. Savi E. Burastero S.E. et al. Omega-5 gliadin anaphylaxis: an integrated diagnostic approach. Eur Ann Allergy Clin Immunol. 2011; 43: 92-94 PubMed Google Scholar We describe the peculiarities of the clinical presentation in 2 elderly patients.

Recombinant high molecular weight‐glutenin subunit‐specific IgE detection is useful in identifying wheat‐dependent exercise‐induced anaphylaxis complementary to recombinant omega‐5 gliadin‐specific IgE test

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a special form of food allergy typically induced by exercise after ingestion of wheat products. We identified wheat omega-5 gliadin and high molecular weight-glutenin subunit (HMW-glutenin) as major allergens for WDEIA and clarified that simultaneous detection of serum IgE binding to synthetic epitope peptides of these allergens identifies more than 90% of WDEIA patients. However, the short synthetic peptides are not suitable for CAP-fluorescent enzyme-immunoassay (CAP-FEIA), which is widely utilized for detecting allergen-specific IgE. In this study, we constructed a CAP-FEIA with recombinant HMW-glutenin, and evaluated its usefulness in identifying the patients with WDEIA. Recombinant HMW-glutenin was expressed as histidine-tag protein in E. coli and purified by histidine-tag affinity column. Wheat, gluten, recombinant omega-5 gliadin, epitope peptide of HMW-glutenin, native and recombinant HMW-glutenin specific IgE in the sera from 48 patients with WDEIA, 16 patients with atopic dermatitis (AD) who had no immediate allergic reaction after wheat ingestion and 12 healthy controls were determined by using CAP-FEIA method. In 16 AD patients without wheat allergy 12 of them (75%) had positive results for native HMW-glutenin test in contrast to epitope peptide of HMW-glutenin (12.5%) and recombinant HMW-glutenin test (12.5%). These results indicate the native HMW-glutenin test has low specificity. Sensitivity and specificity of the IgE test with recombinant HMW-glutenin were 16.7% and 92.9%. These are well compatible with results obtained by using epitope peptide of HMW-glutenin. However, sensitivity and specificity reached to 93.8% and 92.9%, when the test was combined to the test with recombinant omega-5 gliadin. We demonstrated that recombinant HMW-glutenin is best for CAP-FEIA system in point of stability and specificity and confirmed that detection of specific IgE against recombinant HMW-glutenin is useful for diagnosis of WDEIA when combined with the CAP-FEIA (recombinant omega-5 gliadin) test.

Milk and wheat allergy, and celiac disease

Cow's milk, egg, wheat, soy, peanut, and fish account for about 90% of the food allergies but there are considerable differences from one country to another. Milk allergy is among the best characterized food allergies, particularly in infants and small children. Only part of the children with early allergy to cow's milk grow into shool-age with milk allergy but those that do often have severe symptoms and high specific IgE level to milk. In accordance, attaining tolerance to cow's milk is associated with decreased epitope binding by IgE and a concurrent increase in corresponding epitope binding by IgG4. Recent data point that analysis of IgE response to milk components may help in determining those with higher risk for persistent or more severe milk allergy. Among wheat allergic patients, co-sensitization to cow's milk and hen's egg is common. Wheat ingestion may trigger immunoglobulin E (IgE)-mediated immediate symptoms, including urticaria, angioedema, bronchial obstruction, nausea and abdominal pain, or in severe cases, even systemic anaphylaxis. Delayed reactions include gastrointestinal symptoms and worsen-ing of atopic dermatitis. In addition to food allergy, wheat ingestion may cause exercise-induced anaphylaxis, or celiac disease (CD), and inhalation and handling of wheat flour aller-gens may lead to respiratory allergy, or contact urticaria on the skin. Wheat IgE is commonly found in all ages of atopic children when whole grains are used as an antigen either in skin prick tests or serum IgE measurements. The specificity of this IgE re-sponse in identifying clinical disease, however, is poor. It is of importance to recognize dis-ease-determining components in the IgE response. Several studies have shown that sensiti-zation particularly to omega-5 gliadin is associated with challenge-proven wheat-allergy. Moreover, recent data imply that gliadin-positive patients have more likely severe reactions after wheat ingestion. A well-characterized severe clinical entity is also wheat-dependent, ex-ercise-induced anaphylaxis in which sensitization to omega-5 gliadin is a prerequisite. We have analyzed especially the gliadin-sepcific responses in wheat allergy. Sensitization to gliadin with a SPT wheal of ≥5 mm at the time of the diagnostic challenge was associated with a slower course of recovery from wheat hypersensitivity (p = 0.019), and a SPT wheal of ≥ 3 mm to gliadin at any time was associated with the development of asthma. Recently, we examined IgE response to 22 wheat components in children with challenge positive wheat allergy and their controls. The results show that wheat-allergy diagnosis can be improved considerably by component-based ap-proach. In the future, wheat IgE diagnosis should include at least measurement of IgE to gli-adins. Gluten and its major component, gliadin, is essential also in the pathogenesis of celiac dis-ease. Gliadin can be a target of both cellular and humoral immune responses. Approximately 90 percent of patients with celiac disease have the HLA-DQ2 haplotype, explaining the family-association of the disease but still leaving open the wide variability in prevalence between dif-ferent Caucasian populations. Both IgA and IgG antibodies can be seen in CD patients but the most sensitive diagnostic work-up is to define tissue transglutaminase (tTG) transglutami-nase IgA antibodies.

Transformation of the US bread wheat ‘Butte 86’ and silencing of omega-5 gliadin genes

Complex groups of proteins determine the unique functional properties of wheat flour and are sometimes responsible for food intolerances and allergies in individuals that consume wheat products. Transgenic approaches can be used to explore the functions of different flour proteins, but are limited to the few wheat cultivars that can be transformed and also by the lack of detailed information about genes and proteins expressed in grain from those cultivars. The US bread wheat Butte 86 has been extensively characterized and a comprehensive proteome map was developed in which flour proteins were distinguished by mass spectrometry and associated with specific gene sequences. Here, this information has been used to design an RNA interference construct to silence the expression of genes encoding omega gliadins that trigger the food allergy wheat-dependent exercise-induced anaphylaxis (WDEIA). The construct was introduced into immature embryos from Butte 86 using biolistics and bialaphos-resistant plants were regenerated. Stable transformation and inheritance of the transgene were confirmed by PCR. Analysis of proteins in grain from transgenic plants demonstrated that the omega-5 gliadins were either absent or substantially reduced relative to non-transformed controls. The ability to genetically transform Butte 86 makes it possible to alter flour composition in a targeted manner in a commercial US wheat cultivar and should accelerate future research on flour quality and immunogenic potential.

Wheat allergy

This review describes the diverse clinical manifestations of IgE-mediated allergy to ingested wheat and summarizes recent advances in characterization of clinically significant allergens and diagnostic workup. Recent population-based studies have shown the prevalence of wheat allergy and sensitization more precisely than past studies among small populations and in hospital settings. Intensive research has demonstrated the diverse profile of both water/salt-soluble and insoluble allergens involved in clinical types of wheat allergies determined depending on the patient age, the sensitization route, and the protein state during the exposure. Consequently, some new allergens, including nonspecific lipid transfer protein (Tri a 14), have been identified. For diagnosis, the role of water/salt-insoluble gliadins, particularly omega-5 gliadin, a major allergen of wheat-dependent, exercise-induced anaphylaxis, was assessed as compared with the results of oral challenges. The mechanisms of eliciting anaphylactic symptoms by exercise in wheat-dependent, exercise-induced anaphylaxis were speculated upon; one is the allergenicity strengthened by activated tissue transglutaminase and another is the increased absorption of allergens through the gastrointestinal tract. Findings of the recent studies show potential for more precise diagnosis in each clinical type of wheat allergies.

Diagnosing Wheat-Dependent Exercise-Induced Anaphylaxis By Simultaneous Detection of Specific IgE to Gluten, Omega-5 Gliadin and Wheat

Diagnosing Wheat-Dependent Exercise-Induced Anaphylaxis By Simultaneous Detection of Specific IgE to Gluten, Omega-5 Gliadin and Wheat