Diagnosis Of Wheat Allergy Research Articles

Utility of epitope-specific IgE, IgG4, and IgG1 antibodies for the diagnosis of wheat allergy

BackgroundThe bead-based epitope assay (BBEA) has been used to identify epitope-specific (es) antibodies and successfully utilized to diagnose clinical allergy to milk, egg and peanut. ObjectiveThis study aimed to identify es-IgE, es-IgG4 and es-IgG1 of wheat proteins and determine the optimal peptides to differentiate wheat-allergic from wheat-tolerant using the BBEA. MethodsChildren and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled. Seventy-nine peptides from alpha/beta-gliadin, gamma-gliadin (γ-gliadin), omega-5-gliadin (ω-5-gliadin), high and low molecular weight glutenin were commercially synthesized and coupled to LumAvidin beads. Machine learning (ML) methods were used to identify diagnostic epitopes and performance was evaluated using DeLong’s test. ResultsThe analysis includes 122 children (83 wheat-allergic and 39 wheat-tolerant, 57.4% male). ML coupled with simulations identified wheat es-IgE, but not es-IgG4 or es-IgG1 to be most informative for diagnosing wheat allergy. Higher es-IgE binding intensity correlated with the severity of allergy phenotypes, with wheat anaphylaxis exhibiting the highest es-IgE binding intensity. In contrast, wheat-dependent exercise-induced anaphylaxis (WDEIA) showed lower es-IgG1 binding than all other groups. A set of 4 informative epitopes from ω-5-gliadin, and γ-gliadin were the best predictors of wheat allergy with an AUC of 0.908 (sensitivity=83.4%, specificity=88.4%), higher than the performance exhibited by wheat-specific IgE (AUC=0.646, p < 0.001). The predictive ability of our model was confirmed in an external cohort of 71 patients (29 allergic, 42 non-allergic), with an AUC of 0.908 (sensitivity=75.9%, specificity=90.5%). ConclusionThe wheat BBEA demonstrated greater diagnostic accuracy compared to existing specific IgE tests for wheat allergy.

Non-celiac wheat sensitivity: a search for the pathogenesis of a self-reported condition

A significant percentage of the general population reports gastrointestinal and non-gastrointestinal symptoms caused by wheat and/or gluten ingestion, even though they do not suffer from celiac disease (CD) or wheat allergy (WS), because they test negative both for CD-specific serology and histopathology. All patients report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). The objective of this paper was to review some studies regarding the pathogenesis of NCGS to summarize the current hypotheses about the mechanisms, which can lead to NCGS. Particular attention was given to the immunologic and the malabsorptive hypotheses. We reviewed data of our previous studies involving patients diagnosed with NCWS by means of double-blind placebo-controlled wheat challenge. The data indicating a possible wheat allergy diagnosis were examined and other data in the literature were reviewed; we also reviewed the putative role of fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAPs) and of α-amylasetrypsin inhibitors (ATIs) proteins in the NCGS pathogenesis. NCGS pathogenesis has been attributed to very different mechanisms, among others: i) activation of innate and adaptive immunity (the immune/allergic mechanisms) induced by gluten or the non-gluten ATI family; ii) incomplete digestion and/or absorption of FODMAPs (the intolerance mechanisms); and iii) psychological effect.We suggest that NCGS is a heterogeneous condition, which includes different subgroups of patients who have different pathogenic mechanisms: strong data suggest a direct pathogenic immunogenic/inflammatory role of wheat-cereal proteins (not only gluten) in a subgroup, probably the largest, of these patients.

Grass-Allergic Children Frequently Show Asymptomatic Low-Level IgE Co-Sensitization and Cross-Reactivity to Wheat

Background: Specific immunoglobulin E (IgE) sensitization to wheat is more common than a doctor’s confirmed wheat allergy and is also frequently observed in grass pollen-allergic patients (pollinosis patients). Thus, the objective of this study was to investigate the level and feature of serological IgE cross-reactivity between grass pollen and wheat in a cohort of pollinosis subjects with no diagnosis of wheat allergy. Methods: Seventy-two children, aged 5–17 years, with a doctor’s diagnosis of pollinosis, IgE towards grass pollen, and currently eating wheat were recruited. Serum samples were analyzed for IgE against wheat, timothy grass/wheat-specific allergen components, Pru p 3, and cross-reactive carbohydrate determinants (CCD) and specific IgE-binding inhibition experiments were performed. Results: Sixty percent of the grass pollen subjects were sensitized to wheat with a median of 0.5 kU_A/L. Wheat-sensitized subjects were more often sensitized to the two allergens, Phl p 12 and CCD, known to be cross-reactive between grass and wheat. Sensitizations to seven wheat-specific allergens derived from the gluten fraction were, with the exception of one individual, only found in wheat-sensitized subjects. These subjects also more often reported current and past history of allergy to staple foods (milk, egg, wheat, soy, and fish). Conclusion: Wheat sensitization caused by cross-reactivity but also by sensitization to wheat-specific allergens was common in the grass-allergic children and also associated with allergy to staple foods other than wheat. The results indicate the presence of a subgroup of pollinosis patients with simultaneous sensitization to wheat and food allergy not only caused by cross-reactions.

Wheat allergy: diagnosis and management

Triticum aestivum (bread wheat) is the most widely grown crop worldwide. In genetically predisposed individuals, wheat can cause specific immune responses. A food allergy to wheat is characterized by T helper type 2 activation which can result in immunoglobulin E (IgE) and non-IgE mediated reactions. IgE mediated reactions are immediate, are characterized by the presence of wheat-specific IgE antibodies, and can be life-threatening. Non-IgE mediated reactions are characterized by chronic eosinophilic and lymphocytic infiltration of the gastrointestinal tract. IgE mediated responses to wheat can be related to wheat ingestion (food allergy) or wheat inhalation (respiratory allergy). A food allergy to wheat is more common in children and can be associated with a severe reaction such as anaphylaxis and wheat-dependent, exercise-induced anaphylaxis. An inhalation induced IgE mediated wheat allergy can cause baker’s asthma or rhinitis, which are common occupational diseases in workers who have significant repetitive exposure to wheat flour, such as bakers. Non-IgE mediated food allergy reactions to wheat are mainly eosinophilic esophagitis (EoE) or eosinophilic gastritis (EG), which are both characterized by chronic eosinophilic inflammation. EG is a systemic disease, and is associated with severe inflammation that requires oral steroids to resolve. EoE is a less severe disease, which can lead to complications in feeding intolerance and fibrosis. In both EoE and EG, wheat allergy diagnosis is based on both an elimination diet preceded by a tissue biopsy obtained by esophagogastroduodenoscopy in order to show the effectiveness of the diet. Diagnosis of IgE mediated wheat allergy is based on the medical history, the detection of specific IgE to wheat, and oral food challenges. Currently, the main treatment of a wheat allergy is based on avoidance of wheat altogether. However, in the near future immunotherapy may represent a valid way to treat IgE mediated reactions to wheat.

Wheat allergy in children evaluated with challenge and IgE antibodies to wheat components.

Wheat sensitization is common but IgE antibodies (IgE-abs) to wheat are not predictive of clinical symptoms in children with suspected wheat allergy. Wheat allergen components other than ω-5gliadin have not been well studied. Our aim was to characterize the clinical profile and investigate the value of adding measurements of IgE-abs to wheat components in a group of children with a doctor's diagnosed wheat allergy. Sixty-three children with a doctor's diagnosis of wheat allergy confirmed sensitization to wheat and, on a wheat elimination diet, went through oral wheat challenges or had a convincing recent history of wheat allergy. IgE-ab to ω-5 gliadin, low molecular weight glutenin (LMW-glutenin), high molecular weight glutenin (HMW-glutenin) and a native gliadin preparation containing α-, β-, γ-, and ω-gliadin (gliadin) were analyzed. Twenty-six children were positive in challenge, while six children were regarded as wheat allergic due to recent anaphylactic reactions. The IgE-ab levels to all four wheat components were significantly higher in the group with wheat allergy compared to the group with no wheat allergy (p<0.0001). Also, the severity of symptoms at challenge correlated with the IgE-ab levels to all four components (p<0.05). IgE-ab levels to ω-5 gliadin correlated best with challenge outcome, and by additional analysis of gliadin, HMW- and LMW-glutenin IgE-abs all challenge positive children could be identified. Many children diagnosed as wheat allergic have outgrown their allergy and are unnecessarily on a wheat-free diet. The levels of IgE-ab to wheat gluten-derived components correlated well with wheat challenge outcome and severity.

The Editor takes a closer look at some of this month's articles

Clinical & Experimental AllergyVolume 44, Issue 11 p. 1295-1295 Editor's ChoiceFree Access The Editor takes a closer look at some of this month's articles First published: 21 October 2014 https://doi.org/10.1111/cea.12431AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Eosinophils and atopic dermatitis: a direct link with infection Eosinophilic inflammation is a hallmark of the Th2 responses that underpin allergic disease. There is increasing interest in the importance of the microbiota, particularly Staphylococcus aureus and its toxins in driving allergic inflammation. However, there is relatively little information on the mechanisms by which this might occur although a recent study demonstrated that the δ toxin induced mast cell degranulation 1. Fleminger and colleagues (pp. 1335–1346) help to fill this gap by demonstrating that S. aureus exotoxins can interact with eosinophils via CD48, a member of the CD2 family. Interactions via this receptor mediated eosinophil activation and signal transduction. The authors propose CD48 as a potential therapeutic target for atopic dermatitis. Francesca Levi-Schaffer (a) Confocal microscopy of human eosinophils incubated with SA fixed and stained with DAPI (x630; magnification, zoom 2, Zeiss). Bold arrows indicate SA adherent to the eosinophil surface. Thin arrows indicate the internalized bacteria. (b) Human eosinophils incubated with isotype Ab and FITC-labelled SA. (c) CD48 blocked human eosinophils incubated with FITC-labelled SA, exhibiting EETs. [see figure 2a, b, c, in Y. Minai-Fleminger et al. (pp.1335–1346)]. Resolution of airway inflammation: is it down to gamma-delta (γδ) T cells? The mechanisms involved in the resolution of allergic airway inflammation are relatively understudied compared with studies into the cause of the inflammatory response. γδT have previously been shown to downregulate acute inflammatory responses in the lung. In this issue, Murdoch and colleagues (pp. 1386–1398) have studied the role of γδT in remodelling caused by chronic inflammatory responses in mice in a house dust mite model of asthma. They demonstrated that blockade of γδT exacerbated the inflammatory response and led to a greater degree of remodelling changes. The next step is elucidation of the exact mechanism involved to see whether this can be manipulated for therapeutic gain. Jenna Murdoch Sirius red-stained lung sections demonstrating peribronchiolar collagen deposition from Alum and OVA-treated mice treated with either anti-γδTCR or the Ig control antibody, original magnification 40x. [see figure 2d in J. Murdoch et al. (pp. 1386–1398)]. Wheat allergy: distinguishing IgE sensitization from disease Wheat allergy is common, but as with all food allergies IgE sensitization either by skin prick or in vitro testing is relatively non-specific so that food challenge is often necessary to make a clear diagnosis. Mäkelä et al. (pp. 1420–1430) confirmed this observation by showing that while 93% of children suspected of wheat allergy who had an immediate reaction to eating wheat had specific IgE to wheat, so did 43% of children who had no reaction. They then explored in detail whether IgE against one or more of the many allergenic components of wheat would be more informative 2. They identified five components of wheat including alpha amylase inhibitors as giving greater specificity than whole wheat extract, but none of the components were sufficiently specific or sensitive to be useful diagnostically. The diagnosis of wheat allergy remains ‘challenging’. Mika Mäkelä A wheat field. [Photo credit: Bluemoose; Wikimedia Commons]. References 1Nakamura Y, Oscherwitz J, Cease KB et al. Staphylococcus delta-toxin induces allergic skin disease by activating mast cells. Nature 2013; 503: 397– 401. 2Pahr S, Constantin C, Mari A et al. Molecular characterization of wheat allergens specifically recognized by patients suffering from wheat-induced respiratory allergy. Clin Exp Allergy 2012; 42: 597– 609. Caption to cover illustration: The regulatory role of the airway epithelium. (See figure 2 of M. Loxham et al. pp. 1299–1313). This logo highlights the Editor's Choice articles on the cover and the first page of each of the articles. Volume44, Issue11November 2014Pages 1295-1295 ReferencesRelatedInformation

Wheat allergy in children - new tools for diagnostics.

The detection of wheat-specific IgE in children often leads to a suspicion of wheat allergy, but little information is available on the most reliable wheat allergens for predicting clinical reactivity. To evaluate the role of allergenic components of wheat in wheat allergy diagnostics. One hundred and eight children (median age 1.5years; range 0.6-17.3years) with suspected wheat allergy underwent open or double-blinded, placebo-controlled oral wheat challenges. Responsiveness to different allergenic components of wheat was studied by skin prick tests and by determination of serum IgE antibodies using a semi-quantitative microarray assay. Thirty (28%) children reacted with immediate symptoms, and 27 (25%) with delayed symptoms to ingested wheat, whereas 51 (47%) children exhibited no reactions in oral wheat challenges. Positive IgE responses to any of the 12 allergenic components of wheat was seen in 93%, 41%, and 43% of those with immediate, delayed or no reactions to ingested wheat, respectively (P<0.001 to P<0.05 in every comparisons between those with immediate reactions and those with no reactions). Positive IgE responses to ≥5 different allergenic components improved significantly the diagnostic accuracy (with a positive likelihood ratio (LR+) of 5.10). Alpha-amylase inhibitors (AAI), in particular dimeric AAI 0.19 (LR+ 6.12), alpha-, beta-, and gamma-gliadins (LR+ from 3.57 to 4.53), and high-molecular-weight (HMW) glutenin subunits (LR+ 4.37) were the single allergenic components of wheat differentiating most effectively those with immediate symptoms from those who did not exhibit any reactions. Wheat allergy diagnostics is difficult, even using sophisticated component methods. Our results confirm earlier findings about gliadins and identify the dimeric AAI 0.19, as a relevant allergen in clinically reactive patients when compared to non-reactive subjects. The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several components of wheat.

Gluten sensitivity in children: A case report

Objective: The NCGS is a syndrome distinguished by intestinal and/or extra intestinal symptoms which appear within hours or few days after the gluten intake; symptoms disappear quickly with a gluten-free diet and reappear within hours or days from the restatement in subjects in which celiac disease and wheat allergy diagnosis has been excluded. We relate the clinical case of a male subject aged thirteen with chronic abdominal pain, obstinate constipation and recurrent oral aphtae for three years.

Utility Of Probability Curves Using 3gAllergy For Diagnosis Of Wheat Allergy

Previously we presented the utility of allergen specific IgE (sIgE) measurements by 3gAllergy using probability curves for diagnosis of hen’s egg and cow’s milk allergy. In this study, we assessed the utility of probability curves in the diagnosis of wheat allergy.

Combining Analyses of Basophil Allergen Threshold Sensitivity, CD-sens, and IgE Antibodies to Hydrolyzed Wheat, ω-5 Gliadin and Timothy Grass Enhances the Prediction of Wheat Challenge Outcome

Background: Wheat is a common food causing allergy which has implications on the quality of life. The diagnosis of IgE-mediated wheat allergy is based on the clinical history and presence of IgE antibodies (IgE-Ab) in skin or blood, and the results of an oral food challenge which is time consuming and associated with risks. An improved diagnostic workup is needed for wheat allergy. The objective was to examine the relationship between wheat challenge, CD-sens and IgE-Ab to related allergens in wheat-allergic children and investigate if a combination of different markers could enhance the prediction of challenge outcome. Method: Twenty-four children (aged 1-15 years) with a wheat allergy diagnosis underwent an open wheat challenge. CD-sens and IgE-Ab to wheat, hydrolyzed wheat protein (HWP), ω-5 gliadin and timothy grass were analyzed and related to the challenge outcome. Results: A positive challenge was seen in 12/24 children. Children reacting to the challenge had higher IgE-Ab concentrations to wheat, ω-5 gliadin and HWP (p < 0.01) and a tendency to higher wheat CD-sens values (p = 0.08) than nonreacting children. Combining wheat CD-sens >150 and IgE-Ab to wheat >20 kU_A/l, or ω-5 gliadin >0.1 kU_A/l predicted the challenge outcome in 83% of the patients. Most children with IgE-Ab to wheat also had IgE-Ab to timothy. Seven of 9 challenge-positive children had a positive CD-sens to HWP and IgE-Ab to HWP >8 kU_A/l. Conclusion: Combining CD-sens and IgE-Ab to wheat or wheat components could be useful in the diagnosis and follow-up of wheat-allergic children.

Clinical Utility of IgE Antibodies to ω-5 Gliadin in the Diagnosis of Wheat Allergy: A Pediatric Multicenter Challenge Study

Background: There are contradictory results regarding the clinical usefulness of the determination of IgE antibodies to ω-5 gliadin in children with a suspicion of wheat allergy (WA). Methods: The study comprised 311 children and young adults with suspected wheat intolerance treated at three separate pediatric clinics and, with the exception of 25, were found to be positive in specific IgE antibody determinations to wheat. Their ages ranged from 6 months to 20.4 years (median age, 2.3 years). Possible relationships between IgE antibodies to ω-5 gliadin and a physician’s diagnosis of WA and challenge symptoms were studied. Results: The mean concentration of IgE antibodies to ω-5 gliadin was 1.2 kU_A/l in WA patients and <0.35 kU_A/l in patients without WA (p < 0.0001). Seventy-two percent of the WA patients had positive ω-5 gliadin levels and 75% of the patients without WA had negative levels. Logistic regression showed a significant relationship between the probability of WA and the concentration of IgE antibodies to ω-5-gliadin with a 2.6-fold (95% CI: 2.0–3.3) increased risk. Age was an important factor to consider as the risk of WA increased 5.4-fold (95% CI: 1.4–21) for children ≤1 year of age and 2.5-fold (95% CI: 2.0–3.2) for children >1 year of age with increasing levels of IgE. Conclusion: Detection of IgE to ω-5 gliadin seems to be associated with responsiveness to the challenge test and is particularly useful in infants with a suspicion of WA.

Usefulness of specific IgE antibodies to ω-5 gliadin in the diagnosis and follow-up of Japanese children with wheat allergy

Gliadins have been implicated in IgE-mediated allergy to ingested wheat. ω-5 gliadin seems to be a clinically relevant allergen component in children with immediate wheat allergy (WA), but contradictory results have been published. To investigate whether specific IgE (sIgE) antibodies to recombinant ω-5 gliadin could be used as a marker for oral wheat challenge outcome in wheat-sensitized children and to study whether measurements of sIgE to ω-5 gliadin are useful in monitoring children with WA to assess whether the allergy is outgrown or persistent. Eighty-eight serum samples from children sensitized to wheat were collected consecutively. sIgE to ω-5 gliadin was related to a physician's diagnosis of WA. Sixty-seven of 88 children sensitized to wheat were diagnosed as having WA. The geometric mean concentrations of sIgE to ω-5 gliadin were 2.04 kU(A)/L (range, <0.35-100 kU(A)/L) in children with WA and 0.40 kU(A)/L (range, <0.35-1.8 kU(A)/L) in children without WA. At follow-up, after being on a wheat-free diet for approximately 2 years, the sIgE titers to ω-5 gliadin were below 0.35 kU(A)/L (mean, 0.34 kU(A)/L; range, 0.34-2.3 kU(A)/L) in 10 of 15 children with outgrown WA. Conversely, in 12 of 14 children with persistent WA, the sIgE titers to ω-5 gliadin were still elevated (mean, 5.89 kU(A)/L; range, 0.34-16.3 kU(A)/L). sIgE to ω-5 gliadin can be used as an accurate alternative to potentially dangerous wheat food challenges in monitoring WA.

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.

Antigen-Induced Expression of CD203c on Basophils Predicts IgE-mediated Wheat Allergy

For in vitro diagnosis of wheat allergy, specific IgE to wheat is known to be a poor predictive marker. Oral food challenge, the gold standard for the diagnosis, is accompanied by a risk of severe induced reactions. Reliable in vitro tests are needed to be developed for safe indication for oral challenge. We examined the utility of a basophil activation marker, CD203c, for the diagnosis of IgE-mediated wheat allergy. Fifty-eight children with suspected wheat allergy with positive CAP-FEIA to wheat were enrolled. On 70 occasions, the clinical distinction between patients with wheat allergy (WA) and patients tolerant to wheat (TW) was made by means of an oral food challenge test or recent history of immediate allergic reactions or tolerance after ingestion of wheat. Twelve replicate evaluations were performed in 9 patients over more than a 6-month interval. Thirty two patients on 43 occasions were diagnosed with WA and 27 were confirmed to be TW. One patient had both diagnoses 18 months apart. Peripheral blood was incubated with fractionated wheat extracts, purified native omega-5 gliadin (nOG5) and recombinant omega-5 gliadin (rOG5). Expression of CD203c on basophils was then analyzed by flow cytometry using a commercial kit. All wheat proteins induced concentration-dependent enhancement of CD203c expression in WA, but did not in TW. The analysis of receiver operating characteristics (ROC) showed that nOG5-induced CD203c(high)% values provided the best power for discriminating between WA and TW, with a sensitivity of 85.0% and specificity of 77.0% at the cut-off level of 14.4%. AUC for CD203c with nOG5 were significantly higher than that for conventional CAP-FEIA, 0.89 and 0.73, respectively (p < 0.01). Measurement of nOG-induced enhancement of CD203c on basophils is useful for the diagnosis of immediate wheat allergy in children.

Interest of ImmunoCAP System to Recombinant ω-5 Gliadin for the Diagnosis of Exercise-Induced Wheat Allergy

Background: ω-5 gliadin is a major allergen in exercise-induced wheat allergy (EIWA), but it is also implicated in immediate-type reactions to wheat. An ImmunoCAP assay to measure ω-5 gliadin-specific IgE has become available. This study aimed to evaluate this new biological test in wheat allergy diagnosis and to also determine if it was able to discriminate EIWA from other types of wheat allergy. Methods: Sixty-one patients with wheat allergy were divided into 3 groups as a function of their symptoms (EIWA, immediate-type reactions and atopic dermatitis). These patients underwent skin prick tests with purified ω gliadins and ImmunoCAP to wheat flour, gluten and recombinant ω-5 gliadin. Results: The experimental data showed that 78% of EIWA patients had a positive skin prick test to natural ω-5 gliadin and the same proportion had detectable specific IgE to recombinant ω-5 gliadin, indicating that ω-5 gliadin is the main allergen, but not the only one, in our population. Additionally, we showed that this detection was not EIWA specific since ω-5 gliadin-specific IgE was detected in 30% of other patients who had a wheat allergy. These results lead to a positive predictive value of 37.5% and to a negative predictive value of 91%. Conclusions: Although not specific to EIWA, the new ImmunoCAP ω-5 gliadin is an important biological test because of its negative predictive value. In case of food-dependent exercise-induced allergy, the absence of ω-5 gliadin-specific IgE will almost completely exclude the implication of wheat.

IgE antibodies to ω‐5 gliadin associate with immediate symptoms on oral wheat challenge in Japanese children

Gliadins have been implicated in immunoglobulin E (IgE)-mediated allergy to ingested wheat and omega-5-gliadin is known to represent a major allergen in wheat-dependent exercise-induced anaphylaxis. Less known is whether omega-5-gliadin is a clinically relevant allergen in children with immediate allergy to ingested wheat. This study investigates whether specific IgE antibodies to omega-5-gliadin (sIgE-omega-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-omega-5-gliadin was related to symptom severity in children with a positive challenge test. Serum samples from 88 children sensitized to wheat, of whom 35 underwent wheat challenge, were collected consecutively. sIgE-omega-5-gliadin-ab was related to a physician's diagnosis of wheat allergy and challenge symptoms. The mean concentration of sIgE-omega-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-omega-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-omega-5-gliadin-ab compared to children with moderate, mild or no symptoms (P < 0.001). The presence of sIgE-omega-5-gliadin-ab is related to the reaction level to wheat challenge outcome in wheat-sensitized children. The sIgE-omega-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-omega-5-gliadin-ab level may serve as a marker for clinical reactivity in wheat-sensitized individuals.

Wheat allergy: A double-blind, placebo-controlled study in adults

Wheat is believed to be an uncommon cause of food allergy in adults; the number of studies that address IgE mediated wheat allergy in adults is all too few. Determine how many subjects with a history of wheat allergy have real allergy by double-blind, placebo-controlled food challenge; identify the symptoms manifested during the challenge; determine the lowest provocation dose; determine the performance characteristics of wheat skin prick test and specific IgE; identify subjects with real wheat allergy for potential immunoblotting studies. Patients underwent skin test with commercial wheat extract; specific wheat IgE was determined. Subjects were challenged with 25 g wheat. Subjects who were positive to raw wheat challenge underwent cooked wheat challenge. Thirty-seven double-blind placebo-controlled wheat challenges were performed on 27 patients. A total of 13 of 27 (48%) patients had a positive result. Eleven subjects with positive raw wheat challenge underwent cooked wheat challenge: 10 were positive. The provocation dose range was 0.1 to 25 g. Twenty-seven percent of the subjects allergic to wheat had a provocation dose that was < or =1.6 g. Wheat causes real food allergy in adults. More than a quarter of the patients allergic to wheat reacted to less than 1.6 g wheat. Specific IgE was more sensitive than skin test for wheat; however, specificity and predictive values were low for both tests. Thus, these tests should not be used to validate diagnosis of wheat allergy.