Omega-5 Gliadin Research Articles

Allergenic Biomarkers in the Molecular Diagnosis of IgE-Mediated Wheat Allergy.

IgE-mediated wheat allergy can take on various forms, including childhood food allergy to wheat, wheat-dependent exercise-induced anaphylaxis in young adults, baker's respiratory allergy/asthma in workers exposed to wheat flour inhalation, and contact urticaria that is caused by hydrolyzed wheat proteins in some cosmetics, and that is sometimes associated with a food allergy. Singleplex and multiplex immunoassays detect specific IgE antibodies to wheat allergenic molecular biomarkers such as omega-5 gliadin Tri a 19, lipid transfer protein Tri a 14, and alpha-amylase inhibitors. The fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens is a commonly used singleplex assay. Multiplex methods include the ELISA-based macroarray immunoassay using nano-bead technology and a microarray immunoassay on polymer-coated slides. Another promising diagnostic tool is the basophil activation test performed with omega-5 gliadin and other wheat protein types. Detailed comprehension of the structural and immunological features of the numerous wheat allergens significant in clinical settings is imperative for advancing diagnostic biomarkers for IgE-mediated wheat allergies.

Precision allergy molecular diagnosis applications in food allergy.

Precision medicine has become important in the diagnosis and management of food allergies. This review summarizes the latest information regarding molecular allergology, an essential component of food allergy managements. Component-resolved diagnostics (CRD) can be used to investigate sensitization to allergens based on symptoms and to reveal co-sensitization and/or cross-sensitization in patients with allergies. The following allergen components are known to be associated with symptoms: ovomucoid from eggs, omega-5 gliadin from wheat, and many storage proteins (Gly m 8 from soy, Ara h 2 from peanut, Cor a 14 from hazelnut, Ana o 3 from cashew nut, Jug r 1 from walnut, and Ses i 1 from sesame). Recent studies on allergens of macadamia nuts (Mac i 1 and Mac i 2), almonds (Pru du 6), fish (parvalbumin and collagen), and shrimp (Pem m 1 and Pem m 14) have provided additional information regarding CRD. In addition, Pru p 7 is a risk factor for systemic reactions to peaches and has recently been found to cross-react with cypress and Japanese cedar pollen. CRD provides information of individualized sensitization profiles related to symptoms and severity of allergies in patients. Clinical practice based on CRD offers many benefits, such as higher diagnostic accuracy and improved management of individual patients.

Production of omega-5 gliadin monoclonal antibodies for allergenic evaluation of WDEIA-causing wheat varieties

In allergic individuals, ingestion of wheat can lead to wheat-dependent exercise-induced anaphylaxis (WDEIA). Many studies have been conducted to find WDEIA allergen–deficient wheat, including by generating omega-5 gliadin antibodies. However, the reported antibodies have not been specific enough to detect omega-5 gliadins encoded on the 1B chromosome. In this study, we generated monoclonal antibodies against the major allergens causing WDEIA, omega-5 gliadins. Using these antibodies (mono-O5B-1C10), we assessed accumulation of omega-5 gliadins in wild-type and nullisomic-tetrasomic (NT) lines of the wheat (Triticum aestivum) varieties Chinese Spring (CS) by one- and two-dimensional gel electrophoresis, followed by Coomassie blue staining or immunoblotting with mono-O5B-1C10. We also tested mono-O5B-1C10 for major omega-5 gliadins in various wheat germplasms. Our results thus demonstrate the specificity of mono-O5B-1C10 for major omega-5 gliadins and potentially useful for identifying of omega-5 gliadin–deficient wheat varieties that should not cause WDEIA.

Clinical profiles of patients with wheat-induced anaphylaxis at various ages of onset

BackgroundWheat-induced anaphylaxis (WIA) is a serious and potentially life-threatening wheat allergy, more common in adults than in children. Little is known about the differences in clinical profiles in WIA among patients of various ages in China. MethodsWe analyzed data retrospectively from an allergy department in a tertiary hospital that included 248 patients (208 adults and 40 children and adolescents) with a history of WIA. ResultsWe found that alcohol was more frequent in patients aged ≥50 years [older adults] (19.0%, 4/21) than in those aged 12–17 years [adolescents] (0%, 0/33; p = 0.019). The frequency of NSAID use in older adults (42.9%, 9/21) was significantly higher than that in adolescents (0%, 0/33; p < 0.001), and patients aged 18–49 years [young adults] (2.8%, 5/178; p < 0.001). During WIA, cardiovascular symptoms in children were less frequent than those in other age groups (children, 28.6%; adolescents, 87.9%; young adults, 93.0%; older adults, 95.2%; p < 0.001). The consciousness loss rate in adults (both age groups; p < 0.001) and the hypotension rate in older adults (p = 0.006) were higher than those in other age groups. Compared with adults (young and older adults), children had a higher rate of allergic comorbidities (p = 0.004, 0.001, respectively) and a higher rate of other food allergies (p < 0.001, <0.001, respectively). Compared with the mild-to-moderate anaphylaxis group, the severe anaphylaxis group had a higher onset age (p = 0.001), higher cofactor prevalence (p = 0.004), lower allergic comorbidity rate (p = 0.014), and higher positive rate of specific IgE to omega-5 gliadin (ω-5 gliadin) (p = 0.023). ConclusionClinical profiles of patients with WIA are different among various onset age/severity groups. An improved understanding of WIA symptoms in various age/severity groups could help accelerate diagnosis, suggest preventive measures, and contribute to improved patient care.

Toward reducing the immunogenic potential of wheat flour: identification and characterization of wheat lines missing omega-5 gliadins encoded by the 1D chromosome.

Eleven wheat lines that are missing genes for the 1D-encoded omega-5 gliadins will facilitate breeding efforts to reduce the immunogenic potential of wheat flour for patients susceptible to wheat allergy. Efforts to reduce the levels of allergens in wheat flour that cause wheat-dependent exercise-induced anaphylaxis are complicated by the presence of genes encoding omega-5 gliadins on both chromosomes 1B and 1D of hexaploid wheat. In this study, we screened 665 wheat germplasm samples using gene specific DNA markers for omega-5 gliadins encoded by the genes on 1D chromosome that were obtained from the reference wheat Chinese Spring. Eleven wheat lines missing the PCR product corresponding to 1D omega-5 gliadin gene sequences were identified. Two of the lines contained the 1BL·1RS translocation. Relative quantification of gene copy numbers by qPCR revealed that copy numbers of 1D omega-5 gliadins in the other nine lines were comparable to those in 1D null lines of Chinese Spring, while copy numbers of 1B omega-5 gliadins were like those of Chinese Spring. 2-D immunoblot analysis of total flour proteins from the selected lines using a specific monoclonal antibody against the N-terminal sequence of omega-5 gliadin showed no reactivity in regions of the blots containing previously identified 1D omega-5 gliadins. Interestingly, RP-UPLC analysis of the gliadin fractions of the selected lines indicated that the expression of omega-1,2 gliadins was also significantly reduced in seven of the lines, implying that 1D omega-5 gliadin and 1D omega-1,2 gliadin genes are tightly linked on the Gli-D1 loci of chromosome 1D. Wheat lines missing the omega-5 gliadins encoded by the genes on 1D chromosome should be useful in future breeding efforts to reduce the immunogenic potential of wheat flour.

Children with wheat anaphylaxis and with low wheat specific IgE have a different IgE immunoblot pattern than those with high wheat specific IgE.

Children with wheat anaphylaxis can present with a wide range of wheat-specific IgE (sIgE). To identify differences in clinical features and predominant wheat allergens sensitized by these patients. Children with history of wheat anaphylaxis were recruited. Skin prick test (SPT) to wheat, sIgE to wheat, omega-5 gliadin (ω5G), lipid transfer protein (LTP) were investigated. Profiles of IgE-bound wheat allergens were studied to identify predominant wheat allergens. Twenty-nine children (17 males) aged 1-18 years were enrolled. Sixteen patients (55.2%) had wheat-sIgE > 100 kUA/L (WAhi) and 13 patients (44.8%) had wheat-sIgE < 34 kUA/L (WAlo). The median of peak wheat-sIgE in WAhi and WAlo were 340.5 kUA/L (IQR 184.3, 564.5) and 12.2 kUA/L (IQR 1.4, 41.3), respectively. Oral food challenge test (OFC) was carried out in 12 of 13 patients in the WAlo group, all of which had positive results. Eight of these 12 patients developed anaphylaxis during OFC despite having wheat-sIgE less than 10 kUA/L. There were no differences in clinical characteristics and atopic history between WAhi vs. WAlo. Medium to low molecular weight gliadin (< 40 kDa) and glutenin (< 60 kDa) were commonly recognized by patients with WAhi. IgE immunoblot pattern among the WAlo group was more widely dispersed than those with WAhi. Wheat anaphylaxis can occur in patients with low wheat-sIgE. Predominant wheat allergens recognized by patients with WAlo were different than those with WAhi. Such difference could be responsible for anaphylaxis at even low levels of wheat-sIgE.

A potential role of gliadin extract skin prick test in IgE-mediated wheat allergy.

Wheat extracts containing both water/salt and alcohol soluble proteins may increase extract's accuracy for diagnosing IgE-mediated wheat allergy. This study aimed to determine the performance of new invented in-house prepared wheat extracts for skin prick test (SPT). Children aged 1-18 years with history of immediate wheat allergy were recruited. Four in-house prepared wheat extracts (wheat-Coca-10%EtOH, and 3 new invented extracts, wheat-salt, gliadin, and glutenin) and a commercial wheat extract were used for SPT. Serum specific IgE (sIgE) to wheat and omega-5 (ω-5) gliadin were also determined. Oral food challenge (OFC) with wheat flours was performed in all patients except those with history of wheat-induced anaphylaxis or with recent symptoms within the past 6 months. Thirty-one children were recruited. Of those, 14 were excluded from OFC (12 with history of anaphylaxis and 2 with recent symptom). OFC was positive in 8 of 17 children. Of the 5 extracts and sIgE to wheat and ω-5 gliadin, gliadin extract provided the best SPT performance with 84.2% sensitivity, 88.9% specificity, 94.1% positive predictive value (PPV), 72.7% negative predictive value (NPV), 7.59 positive likelihood ratio (LR), 0.18 negative LR, and 85.7% accuracy. Compared to other in-house and commercial wheat extracts and sIgE to wheat and ω-5 gliadin, SPT with an in-house gliadin extract yielded the highest performance for the diagnosis IgE-mediated wheat allergy.

Cofactors, age at onset, allergic comorbidities and gender are different in patients sensitized to omega-5 gliadin and Pru p 3

Aim of this study is to clarify the impact of cofactors on allergic reactions in patients sensitized to LTP and ω-5-gliadin. We retrospectively examined the charts of our outpatients from January 2015 to July 2019 and identified 157 patients seen for urticaria/angioedema or anaphylaxis after a meal, in presence or absence of cofactors and sensitized to LTPs (Pru p 3 and/or Tri a 14) and/or ω-5-gliadin (Tri a 19). we compared LTPs-positive patients and those sensitized to Tri a 19 in order to assess the difference in cofactors involved and in frequency of clinical presentation. Our data show that exercise is the most frequent cofactor in FDEIAn and the involvement of exercise, alcohol and multiple cofactors was more frequently found in males than in females. We found that exercise, pollen counts peaks and multiple cofactors were more often related to anaphylaxis than mild reactions. Finally, we performed a comparison between patients LTPs+ and Tri a 19+ that showed in the latter group a lower frequency of allergic comorbidities, a higher median age at the onset of symptoms and frequency of alcohol exposure. Our data show that the search for possible cofactors involved in food allergy is essential not only for diagnostic purposes, but also for risk assessment strategies.

Phenotypic Distinctions Between Omega-5-Gliadin Allergy and Peanut Allergy: Clinical Profile, Reaction Rates and Triggers, and Quality of Life.

Different phenotypes of food allergy may exist, exhibiting distinct clinical features, and driven by different pathogenic mechanisms. We compared omega-5-gliadin (O5G) allergy to peanut allergy, focusing on clinical features, reaction rates and triggers, and quality of life (QOL). We surveyed adults with O5G allergy and peanut allergy regarding their diagnosis, co-morbidities, allergic reactions, and QOL measured by the FAQLQ-AF. We received responses from 43/80 (54%) individuals with O5G allergy and 43/130 (33%) with peanut allergy. Compared to peanut allergic individuals, those with O5G allergy were older at age of onset (37.2 vs 2.5 years, p < 0.001), had fewer additional atopic conditions (0.88 vs 2.93, p < 0.001) or food allergies (0.15 vs 1.86, p < 0.001), and more frequent reactions before diagnosis (1.085 vs 0.29 per month, p < 0.05) Reaction rates improved in both groups following diagnosis. Reactions to peanut were more often triggered by accidental exposure (84% vs 26%, p < 0.001) and being away from home (65% vs 28%, p < 0.001), while reactions to O5G were more often due to deliberate ingestion (30% vs 9%, p < 0.05) or unexpected exercise (35% vs 2%, p < 0.001). Overall QOL score was similar between groups (4.2 in O5G allergy, 4.7 in peanut allergy, p = 0.12), but worse among women and those with additional food allergies. Phenotypic differences between O5G and peanut allergy support the development of different clinical approaches and the possibility of targeting distinct pathogenic mechanisms for prevention and treatment. Quality of life was impaired to a similar degree between groups.

Omega-5 and Gamma Gliadin are the Major Allergens in Adult-Onset IgE-Mediated Wheat Allergy: Results from Thai Cohort with Oral Food Challenge.

BackgroundVarious clinical patterns based on routes of sensitization and sensitized allergens are reported in adult-onset IgE-mediated wheat allergy. There is still a paucity of data on IgE-bound wheat allergen profiles in wheat challenge-proven adult-onset wheat allergic cases. Therefore, we aim to identify the major sensitized allergens in Thai adult-onset wheat allergic patients whose first symptom occurred after the age of 18 years despite previous tolerance.MethodsThis cross-sectional pilot study recruited patients from the Thai Adult-onset IgE-mediated Wheat Allergy Cohort (TAWAC). The sera of patients with mostly challenge-proven cases were selected for allergen study, including ImmunoCAP and IgE-bound gliadins along with glutenins profiles. The IgE-bound proteins were identified by liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). Direct binding of IgE to recombinant gliadin and glutenin was performed to confirm the results of immunoblot and LC-MS/MS.ResultsEleven wheat-dependent exercise-induced anaphylaxis (WDEIA) and 4 typical wheat allergy (WA) patients were enrolled. Serum IgE from >50% of bound proteins had a molecular weight ranging from 35 to 55 kDa in both gliadin and glutenin extracts. Further, ELISA demonstrated that γ-gliadin and ω5-gliadin were the most important major allergens. Other major allergens include α/β-gliadin, HMW glutenin, and possibly α-amylase inhibitor or LWM glutenin. Gamma-gliadin sensitization was found in all WA patients (4/4), while ω-5 gliadin was found in all WDEIA patients (11/11) from ELISA.ConclusionWheat γ-gliadin and ω-5 gliadin are major wheat allergens among adult-onset wheat allergy patients in Thailand. Component-resolved diagnosis using γ-gliadin might be helpful in high suspicion of wheat allergy.

Utilization of Component-Resolved Diagnosis in Precision Allergology

It is very important to identify the causal allergen of each patient in the diagnosis and treatment of allergic diseases. An experimental method of specific IgE testing for single clinically meaningful antigens is called component resolved diagnosis (CRD). Since the introduction of CRD, many single antigens with clinical significance from animal and plant allergenic source have become known. Bet v 1, the major allergen of white birch pollen, can be an indication marker for allergen-specific immunotherapy if the patient is sensitized. Phl p 1, the group I allergen of timothy grass pollen, is an important marker that suggests that patients are truly sensitized to grass pollen. The major allergen of ragweed pollen, Amb a 1 and Art v 1, which is the major allergen of mugwort pollen, are clinically important to distinguish true sensitization. House dust mites have several clinically useful component allergens. Der p 1 and Der p 2 are the initiation molecules in the molecular spreading of allergic diseases caused by house dust mites. Among food allergens, Ara h 2 from peanut, which is closely related to anaphylaxis among several clinical manifestation of peanut allergy. Tri a 19, well known to omega-5 gliadin is important in patients with wheat-dependent exercise-induced anaphylaxis. It is conceivable that the molecular biological concept of CRD methods should lead to ‘patient-customized treatment’ beyond ‘diagnosis’ in the future. Primary prevention of the allergic diseases will apply, which will conceptually be called ‘allergen immunprophylaxis’. This is the right direction of future precision allergology.

Differences in omega-5-gliadin allergy: East versus West.

BackgroundOmega-5-gliadin (O5G) allergy, also known as wheat-dependent exercise-induced anaphylaxis, is commonly reported in the Western, but not Asian, populations. Although significant differences in O5G allergy presentation across different populations are likely but there have been no previous reports on this important topic.ObjectiveTo report on the prevalence and characteristics of O5G allergy in Hong Kong (HK) compared with the United Kingdom (UK).MethodsO5G allergy patients attending Queen Mary Hospital (HK cohort), and Guy's and St Thomas' Hospital, London (UK cohort) were studied and compared.ResultsA total of 46 O5G allergy patients (16 HK; 30 UK) were studied. In the HK cohort, 55% of all patients previously labeled as “idiopathic anaphylaxis” were diagnosed with O5G allergy. Exercise was the most common cofactor in both cohorts, followed by alcohol and nonsteroidal anti-inflammatory drugs (NSAID). A higher proportion of the HK cohort reported NSAID as a cofactor (13% vs. 0%, p = 0.048). In the HK cohort, more patients presented with urticaria and cardiovascular manifestations (100% vs. 77%, p = 0.036; 100% vs. 70%, p = 0.015, respectively); the range of presentation was more diverse in the UK cohort. In HK fewer patients adhered to wheat avoidance (50% vs. 87%, p = 0.007) and more patients avoided cofactors only (44% vs. 10%, p = 0.008).ConclusionO5G allergy appears relatively underdiagnosed in HK. Urticaria and cardiovascular manifestations are common; NSAID plays an important role as a cofactor and patients are less concordant with dietary avoidance measures than in the Western population.

Omalizumab in the treatment of wheat-dependent exercise-induced anaphylaxis: Case report

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a rare but possibly fatal condition. Patients with WDEIA may have severe difficulty for controlling their symptoms as the level of exercise, that can potentially trigger an anaphylaxis, may be very low. We, herein, report two patients with severe chronic spontaneous urticaria who subsequently developed WDEIA. Their symptoms occurred within minutes of walking at a slow pace after eating wheat-containing meals. Diagnosis were confirmed by positive omega-5 gliadin, gluten and wheat flour-specific IgE results. They have received omalizumab mainly for controlling their urticaria-related symptoms, but significant benefit has been obtained in regards to their exercise tolerance as well as their urticaria after the first injection of omalizumab. We have discussed the beneficial effects of omalizumab in these cases. However, additional clinical evidence would be needed for using omalizumab as a possible treatment option in WDEIA.

A Case of Wheat-Dependent Exercise Induced Anaphylaxis (WDEIA)

Wheat dependent exercised induced anaphylaxis (WDEIA) is common in Asian adult populations especially in northern China and Korea. A classical WDEIA case is presented with detailed histories, investigations and management plans. Serum specific IgE to omega-5 gliadin is critical for the diagnosis of WDEIA. Avoidance from wheat and exercise are the keys for prevention of anaphylaxis. Omalizumab, a monoclonal antibody against IgE, is reserved for cases with recurrent anaphylaxis and active physical activity status and it is an off-label treatment.

Genomics Approach to Identify the Cause of the Missing Omega-5 Gliadin Protein in O-Free Wheat

A previous work developed and identified a new omega-5 gliadin deficient wheat line named O-free by crossing Keumkang and Olgeuru, which is nutritionally quite meaningful in that omega-5 gliadin is one of the known wheat allergens. To verify the characteristics of the O-free, we performed RNA sequencing (RNAseq) analysis of the O-free and the two parent lines (Keumkang and Olgeuru). The results of the similarity analysis with the ESTs for gliadins and glutenins showed that the O-free ESTs had no similarity with the omega-5 gliadin sequences but had similarity to other gliadins and glutenins. Furthermore, mapping results between the raw RNAseq data from the O-free and the omega-5 gliadin sequence showed a clear deletion of the N-terminal sequences which are an important signature of omega-5 gliadin. We also designed specific PCR primers that could identify omega-5 gliadin in the genomic DNA. The results showed that no omega-5 gliadin fragments were detected in the O-free. According to these results, we confirmed that the deficiency of omega-5 gliadin in the O-free is not caused by post-transcriptional or post-translational regulations such as epigenetic phenomena but by a simple deletion in the chromosome. Furthermore, we showed that the low-molecular weight glutenin subunit (LMW-GS) gene in the O-free had a single nucleotide polymorphism (SNP) causing a premature stop codon, resulting in a truncated polypeptide. We expect that the O-free line may serve as an excellent source of wheat that could prevail in the hypo-allergen wheat market, which has recently gained interest world-wide.

Towards reducing the immunogenic potential of wheat flour: omega gliadins encoded by the D genome of hexaploid wheat may also harbor epitopes for the serious food allergy WDEIA

BackgroundOmega-5 gliadins are a group of highly repetitive gluten proteins in wheat flour encoded on the 1B chromosome of hexaploid wheat. These proteins are the major sensitizing allergens in a severe form of food allergy called wheat-dependent exercise-induced anaphylaxis (WDEIA). The elimination of omega-5 gliadins from wheat flour through biotechnology or breeding approaches could reduce the immunogenic potential and adverse health effects of the flour.ResultsA mutant line missing low-molecular weight glutenin subunits encoded at the Glu-B3 locus was selected previously from a doubled haploid population generated from two Korean wheat cultivars. Analysis of flour from the mutant line by 2-dimensional gel electrophoresis coupled with tandem mass spectrometry revealed that the omega-5 gliadins and several gamma gliadins encoded by the closely linked Gli-B1 locus were also missing as a result of a deletion of at least 5.8 Mb of chromosome 1B. Two-dimensional immunoblot analysis of flour proteins using sera from WDEIA patients showed reduced IgE reactivity in the mutant relative to the parental lines due to the absence of the major omega-5 gliadins. However, two minor proteins showed strong reactivity to patient sera in both the parental and the mutant lines and also reacted with a monoclonal antibody against omega-5 gliadin. Analysis of the two minor reactive proteins by mass spectrometry revealed that both proteins correspond to omega-5 gliadin genes encoded on chromosome 1D that were thought previously to be pseudogenes.ConclusionsWhile breeding approaches can be used to reduce the levels of the highly immunogenic omega-5 gliadins in wheat flour, these approaches are complicated by the genetic linkage of different classes of gluten protein genes and the finding that omega-5 gliadins may be encoded on more than one chromosome. The work illustrates the importance of detailed knowledge about the genomic regions harboring the major gluten protein genes in individual wheat cultivars for future efforts aimed at reducing the immunogenic potential of wheat flour.

ADULT-ONSET WHEAT ANAPHYLAXIS IN THE POSTPARTUM PERIOD

Introduction Although most food allergies present in childhood, food allergies can develop at any age. The lay press suggests the occurrence of new allergy following parturition, but this has not been well-documented in the literature. Case Description 37-year old female without prior food allergies presented with sudden-onset urticaria, one week postpartum, which resolved with epinephrine. Over the subsequent two weeks, she had two episodes of anaphylaxis, during walks preceded by wheat ingestion. Per the patient's report, ingestion of wheat without exercise did not provoke symptoms. Skin testing shortly thereafter to a panel of aeroallergens and food allergens was negative. Serum specific IgE testing and component-resolved diagnostics were significant only for wheat omega-5 gliadin (5.3 ISU-E). An open challenge to wheat was positive with urticaria. We recommended strict avoidance of wheat. On follow up in 4 years, she had had no further allergic reactions and continued to avoid wheat. Omega-5 gliadin sensitization has declined slightly over these four years, to 2.1 ISU-E. She has not been re-challenged to wheat. Discussion Recent anaphylaxis may yield falsely-negative skin test results. This patient's initial history was suggestive of food-dependent, exercise-induced anaphylaxis (FDEIA). Wheat sensitization, specifically omega-5 gliadin, is the most commonly reported sensitization and trigger in FDEIA. Although exercise was a previously required component of her reactions, our patient developed subsequently a reaction during the open challenge, which was at rest. Striking in this case was the development of new food allergy closely associated with parturition. Pregnancy could modify food allergy risk.

Multicenter, randomized, double-blind, placebo-controlled clinical trial of vital wheat gluten oral immunotherapy

Wheat is a common food allergen that can cause anaphylaxis. We sought to determine the efficacy and safety of vital wheat gluten (VWG) oral immunotherapy (OIT). After baseline double-blind, placebo-controlled food challenge (DBPCFC), 46 patients with wheat allergy (median age, 8.7years; range, 4.2-22.3years) were randomized 1:1 to low-dose VWG OIT or placebo, with biweekly escalation to 1445mg of wheat protein (WP). After a year 1 DBPCFC, active subjects continued low-dose VWG OIT for another year and underwent a year 2 DBPCFC and, if passed, a subsequent off-therapy DBPCFC. Placebo-treated subjects crossed over to high-dose VWG OIT (maximum, 2748mg of WP). The median baseline successfully consumed dose (SCD) was 43mg of WP in both groups. At year 1, 12 (52.2%) of 23 low-dose VWG OIT-treated and 0 (0%) of 23 placebo-treated subjects achieved the primary end point of an SCD of 4443mg of WP or greater (P<.0001); median SCDs were 4443 and 143mg, respectively. At year 2, 7 (30.4%) of 23 low-dose VWG OIT-treated subjects were desensitized to an SCD of 7443mg of WP; 3 (13%) achieved sustained unresponsiveness 8 to 10weeks off therapy. Among placebo-treated subjects who crossed over to high-dose VWG OIT, 12 (57.1%) of 21 were desensitized after 1year (median SCD, 7443mg of WP; nonsignificant vs low-dose VWG OIT). At year 1, skin prick test responses and wheat- and omega-5 gliadin-specific IgE levels did not differ between groups; the low-dose VWG OIT median specific IgG4 level was greater than placebo (wheat, P=.0005; omega-5 gliadin, P=.0001). Year 1 SCDs correlated with wheat-specific (rho=0.55, P=.0003) and omega-5 gliadin-specific (rho=0.51, P=.001) IgG4 levels in all subjects. Among 7822 low-dose VWG OIT doses in year 1, 15.4% were associated with adverse reactions: 0.04% were severe, and 0.08% subjects received epinephrine. Among 7921 placebo doses, 5.8% were associated with adverse reactions; none were severe. Low- and high-dose VWG OIT induced desensitization in about one half of the subjects after 1year of treatment. Two years of low-dose VWG OIT resulted in 30% desensitization, and 13% had sustained unresponsiveness.

A New Diagnostic Criteria of Wheat-Dependent, Exercise-Induced Anaphylaxis in China

Background:Wheat-dependent, exercise-induced anaphylaxis (WDEIA) is an allergic reaction induced by intense exercise combined with wheat ingestion. The gold standard for diagnosis of WDEIA is a food exercise challenge; however, this test is unacceptable for Chinese WDEIA patients and unable to be approved by the Ethics Committee of Chinese hospitals due to substantial risk. There are no diagnostic criteria for Chinese WDEIA patients. The aim of present study was to propose new practical diagnosis criteria for Chinese WDEIA patients.Methods:We prospectively included 283 clinically diagnosed WDEIA patients from January 1, 2010 to June 30, 2014, and in the meanwhile, three groups were enrolled which included 133 patients with the history of anaphylaxis induced by food other than wheat, 186 recurrent urticaria patients, and 94 healthy participants. Clinical comprehensive evaluation by allergists used as the reference gold standard, receiver operator characteristic (ROC) curves were plotted, areas under curve (AUC) for specific immunoglobin E (sIgE) were compared to evaluate the diagnostic value of IgE specific to wheat, gluten, and ω-5 gliadin. Patients were followed up by telephone questionnaire 1 year after diagnosis.Results:We reviewed 567 anaphylactic reactions in 283 WDEIA patients. Of these anaphylactic reactions, 415 (73.3%) reactions were potentially life-threatening anaphylaxis. Among the 567 anaphylactic reactions, 75% (425/567) occurred during exercise. The highest AUC (0.910) was observed for sIgE for gluten, followed by omega-5 gliadin (AUC 0.879). Combined gluten- and ω-5 gliadin-specific IgE testing provided sensitivity and specificity of 73.1% and 99.0%, respectively. During the 1-year follow-up period, repeat anaphylaxis was rare when patients observed strict avoidance of wheat products combined with exercise or other triggering agents.Conclusions:In this study, we proposed diagnostic criteria and management of WDEIA patients in China. Our present study suggested that confirmed anaphylactic reactions triggered by wheat with positive sIgE to gluten and omega-5-gliadin may provide supportive evidence for clinicians to make WDEIA diagnosis without performing a food exercise challenge.

Screening and Identification of Omega-5 Gliadin Mutants in Wheat Doubled-Haploid Lines

Screening and Identification of Omega-5 Gliadin Mutants in Wheat Doubled-Haploid Lines