Wheat-dependent Exercise-induced Anaphylaxis Research Articles

The top 100 most cited articles in the past 30 years of wheat allergy: a bibliometric analysis.

Wheat allergy (WA), characterized by immunological responses to wheat proteins, is a gluten-related disorder that has become increasingly recognized in recent years. Bibliometrics involves the quantitative assessment of publications within a specific academic domain. We aimed to execute an extensive bibliometric study, focusing on the past 30 years of literature related to wheat allergy. We searched the Web of Science database on 5th Dec 2023. We used the keywords "wheat allergy or wheat anaphylaxis or wheat hypersensitivity," "gliadin allergy or gliadin anaphylaxis or gliadin hypersensitivity," "wheat-dependent exercise-induced anaphylaxis," and "baker's asthma" for our search. All items published between 1993 and 2023 were included. The top 100 most cited articles were identified and analyzed. Our study conducted an in-depth bibliometric analysis of the 100 most-cited articles in the field of wheat allergy, published between 2002 and 2019. These articles originated from 20 different countries, predominantly Japan and Germany. The majority of these articles were centered on the pathogenesis and treatment of wheat allergy (WA). The Journal of Allergy and Clinical Immunology (JACI) was the most prolific contributor to this list, publishing 14 articles. The article with the highest citation count was published by Biomed Central (BMC) and garnered 748 citations. The peak citation year was 2015, with a total of 774 citations, while the years 1998, 2001, and 2005 saw the highest publication frequency, each with 7 articles. Our study aims to provide physicians and researchers with a historical perspective for the scientific progress of wheat allergy, and help clinicians effectively obtain useful articles that have a significant impact on the field of wheat allergy.

Effective and safe provocation test for wheat-dependent exercise-induced anaphylaxis (WDEIA) in adults results of testing on 33 cases

Effective and safe provocation test for wheat-dependent exercise-induced anaphylaxis (WDEIA) in adults results of testing on 33 cases

Wheat-free diet alters the intestinal microbiome structure of patients with wheat-dependent exercise-induced anaphylaxis

Wheat-free diet alters the intestinal microbiome structure of patients with wheat-dependent exercise-induced anaphylaxis

Identification of RNAi hypoallergic bread wheat lines for wheat-dependent exercise-induced anaphylaxis patients.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is one of the most severe forms of wheat allergy. It occurs in patients when they exercise after ingesting wheat-containing foods. Nowadays, the only possible alternative for WDEIA patients is to avoid such foods. This study investigated the potential of six RNA of interference (RNAi) wheat lines with low-prolamin content as alternatives for WDEIA patients. For that purpose, a high performance-liquid chromatography (HPLC) analysis was performed to evaluate differences in gluten protein fractions among these lines. Next, western blots were conducted to measure the immunoglobulin E (IgE) reactivity to wheat proteins in sera from five WDEIA patients. Additionally, monoclonal antibodies (moAb) recognition sites and the IgE binding sites were searched in all peptides identified by LC-MS/MS after protein digestion. The results showed a 61.4%-81.2% reduction in the gliadin content of the RNAi lines, accompanied by an increase in their high-molecular weight (HMW) glutenin content compared to the wild type bread wheat line (WT). In all cases, the reduction in gliadin content correlated with a decrease in IgE reactivity observed in the sera of WDEIA patients, highlighting the E82 and H320 lines. These two RNAi lines exhibited a ≤90% reduction in IgE reactivity. This reduction could be attributed to an absence of IgE binding sites associated with α- and ω5-gliadins, which were present in the WT. Overall, these lines offer a potential alternative for foodstuff for individuals with WDEIA.

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.

Epidemiology, outcomes, and disproportionate burden of food-dependent exercise-induced anaphylaxis from the Hong Kong Multidisciplinary Anaphylaxis Management Initiative (HK-MAMI).

Anaphylaxis is a life-threatening allergic reaction that poses a considerable burden on populations across all ethnicities and age groups. The Hong Kong Multidisciplinary Anaphylaxis Management Initiative (HK-MAMI) was established to streamline the assessment of patients with anaphylaxis via a multidisciplinary and protocol-driven approach. This prospective study aims to define the etiology, clinical manifestations, and treatment of patients with anaphylaxis in Hong Kong. Prospective clinical data from allergologic investigations from patients who completed evaluation by the HK-MAMI pathway between January 2017 and August 2022 were analyzed. Of the 161 patients referred via the HK-MAMI, 131 (81.4%) met the diagnostic criteria for anaphylaxis. The median delay in diagnosis was 2 years (range 0-30 years). The majority of anaphylaxis cases were attributed to food-dependent exercise-induced anaphylaxis (FDEIA), especially wheat-dependent exercise-induced anaphylaxis. In acute management settings, paired tryptase samples were taken in only around one-third of anaphylaxis cases, with 82.5% of the samples demonstrating significant elevation. There was a general underprescription of adrenaline autoinjectors, especially for food-related anaphylaxis. Patients with FDEIA had later ages of onset and diagnosis, and they presented with more cardiovascular manifestations. Skin prick tests and specific IgE level tests were able to diagnose 95% of FDEIA cases. Our study highlights the significant burden of FDEIA, and especially WDEIA, in Hong Kong, its association with severe presentations, and difficulties encountered in emergency or primary care settings. We advocate appropriate adrenaline use during acute-care management and discharge plans, as well as taking serum mast cell tryptase samples during acute episodes. Interdisciplinary collaboration remains crucial to upholding proper and optimized care for patients with anaphylaxis in Hong Kong.

Alpha/Beta Gliadin MM1 Is a Novel Antigen for Wheat-Dependent Exercise-Induced Anaphylaxis

Introduction: Screening for ω-5 gliadin specific IgE antibody (sIgE) has high diagnostic utility in cases of suspected wheat-dependent exercise-induced anaphylaxis (WDEIA); however, negative cases may require confirmatory tests, such as the oral challenge test. Thus, newly identified allergens that can be used for the serological diagnosis of WDEIA are needed. This study aimed to identify additional sIgE biomarkers of WDEIA. Methods: Forty-two patients with WDEIA (5 negative/37 positive for ω-5 gliadin sIgE) were enrolled. For comparison, 8 patients with immediate-type wheat allergy without WDEIA and 20 healthy controls without wheat allergy were also enrolled. Extracted wheat proteins were separated by 2D-PAGE. Proteins that reacted with serum IgE antibody in 2D Western blotting (2D-WB) were identified using mass spectrometry. Recombinant proteins were synthesized in Escherichia coli, and the antigenicity was tested using ELISA and the basophil activation test. Results: In 2D-WB, nine proteins reacted with the serum IgE antibody from at least 60% of patients with WDEIA (n ≥ 25/42). ELISA revealed that alpha/beta gliadin MM1 exhibited the highest positive immunoreactivity in 23 of 26 patients who were positive for ω-5 gliadin sIgE (88%) and in 5 of 5 patients who were negative for ω-5 gliadin sIgE (100%). Alpha/beta gliadin MM1 exhibited significantly higher basophil activation in 14 patients with WDEIA when compared to 5 individuals without a wheat allergy. Conclusions: Alpha/beta gliadin MM1 sIgE exhibited the highest seropositivity, even among patients who were negative for ω-5 gliadin sIgE. The inclusion of alpha/beta gliadin MM1 in allergen-sIgE tests may improve the sensitivity for diagnosing WDEIA.

Wheat-dependent exercise-induced anaphylaxis: subtypes, diagnosis, and management.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is an IgE-mediated food allergy with allergic symptoms ranging from intermittent urticaria to severe anaphylaxis that occurs when wheat ingestion is combined with augmenting cofactors such as exercise, non-steroidal anti-inflammatory drugs, or alcohol. In most cases, patients are identified by sensitization to ω5-gliadins in the gluten fraction of wheat. ω5-gliadin-negative subtypes of WDEIA are often difficult to diagnose and may be caused by Tri a 14 (wheat lipid transfer protein), after percutaneous sensitization with hydrolyzed wheat proteins, or, in rare cases, by cross-reactivity to grass pollen. Diagnosis is established based on the patients' history in combination with serum IgE profile, skin testing, basophil activation tests, and challenge tests with cofactors. Individual dietary counselling remains the central pillar in the management of WDEIA patients. A completely wheat-free diet is a possible option. However, this appears to promote tolerance less than continued regular consumption of gluten-containing cereals in the absence of cofactors. All patients should have an emergency set for self-treatment including an adrenaline autoinjector and receive adequate instruction. More data are needed on sublingual immunotherapy for WDEIA, a potentially promising therapeutic prospect. This article provides an overview of current knowledge on the diagnosis and management of WDEIA including an optimized challenge protocol using wheat gluten and cofactors.

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.

A Narrative Mini Review on Current Status of Hypoallergenic Wheat Development for IgE-Mediated Wheat Allergy, Wheat-Dependent Exercise-Induced Anaphylaxis

Immunoglobulin E (IgE)-mediated food allergies to wheat that develop after school age typically shows a type of wheat-dependent exercise-induced anaphylaxis (WDEIA). At present, avoidance of wheat products or postprandial rest after ingesting wheat is recommended for patients with WDEIA, depending on the severity of the allergy symptoms. ω5-Gliadin has been identified as the major allergen in WDEIA. In addition, α/β-, γ-, and ω1,2-gliadins, high and low molecular weight-glutenins, and a few water-soluble wheat proteins have been identified as IgE-binding allergens in a small proportion of patients with IgE-mediated wheat allergies. A variety of approaches have been manufactured to develop hypoallergenic wheat products that can be consumed by patients with IgE-mediated wheat allergies. In order to analyze such approaches, and to contribute to the further improvement, this study outlined the current status of these hypoallergenic wheat productions, including wheat lines with a reduced allergenicity that are mostly constructed for the patients sensitized to ω5-gliadin, hypoallergenic wheat by enzymic degradation/ion exchanger deamidation, and hypoallergenic wheat by thioredoxin treatment. The wheat products obtained by these approaches significantly reduced the reactivity of Serum IgE in wheat-allergic patients. However, either these were not effective on some populations of the patients, or low-level IgE-reactivity to some allergens of the products was observed in the patients. These results highlight some of the difficulties faced in creating hypoallergenic wheat products or hypoallergenic wheat lines through either traditional breeding or biotechnology approaches in developing hypoallergenic wheat completely safe for all the patients allergic to wheat.

Prospects for the treatment of gluten-associated diseases: on our daily bread, celiac disease, gluten proteins and more…

Food safety all over the world is largely dependent on production of grains that are cultivated in 60% of agricultural lands. Wheat is the main food for millions of people and one of the three most commonly cultivated grain cultures worldwide, along with corn and rice. Modern wheat is a product of gene engineering interventions aimed at increased productivity, yields, nutrient quota, and storage time, as well as immunogenic properties. However, the consumption of gluten, a proline and glutamine-rich wheat, rye and barley protein, triggers gluten-dependent disorders, such as celiac disease, wheat allergy, baker's asthma and wheat-dependent exercise-induced anaphylaxis. This group of disorders are curable provided the correct diagnosis has been made and strict lifelong gluten-free diet is implemented. Continuous patient's adherence to the gluten-free diet is associated with a number of medical and paramedical challenges, and the adherence level of the most compliant patients does not exceed 80%. The paper discuss other treatment strategies to improve the nutrition of people with gluten-sensitive disorders, in particular, the reduction grain gluten content, gluten sequestration in the gut before its digestion, prevention of gluten absorption and subsequent immune cell activation, and administration of tissue transglutaminase 2 inhibitors.

Efficacy and safety of omalizumab in adult patients with wheat-dependent exercise-induced anaphylaxis: Reduction of in vitro basophil activation and allergic reaction to wheat

BackgroundIn patients with wheat-dependent exercise-induced anaphylaxis (WDEIA), anaphylactic shock occurs frequently, therefore avoidance of wheat products is recommended. We aimed to evaluate efficacy and safety of long-term omalizumab treatment for adult patients with WDEIA. MethodsIn this phase 2, multicentre single-arm trial, 20 adult patients with WDEIA were enrolled (UMIN 000019250). All patients were administered 150–600 mg of omalizumab subcutaneously and evaluations (basophil activation and blood examination) were performed at regular intervals during administration period (0–48 weeks) and observation period (48–68 weeks). Primary endpoint was proportion of the patients who achieved a basophil activation rate below 10% with fractionated wheat preparations, and secondary endpoint was proportion of the patients with no allergic reactions after wheat products ingestion. ResultsDuring the omalizumab treatment, more than 80% of the patients achieved the basophil activation rate less than 10% against all fractionated wheat preparations, and 68.8% of the patients who achieved the primary endpoint experienced no allergic reaction. During the observation period, the proportion of the patients who achieved a basophil activation rate below 10% decreased gradually, and the proportion of patients with positive allergic reactions increased gradually thereafter and reached maximum of 46.7%. Severe adverse events were not observed during the study. ConclusionsLong-term omalizumab treatment is safe and effective for adult patients with WDEIA when assessed by basophil activation rate with wheat allergens as well as allergic reactions after lifting of restrictions on wheat intake. However, this is not enough to achieve desensitization.

Idiopathic Anaphylaxis? Analysis of Data from the Anaphylaxis Registry for West Pomerania Province, Poland.

The most common causes of anaphylaxis, according to various authors and depending on the age of the studied groups, are: Hymenoptera venom, food, and medications. Unfortunately, we are not always able to indicate the cause of anaphylaxis. There are data in the literature where as many as 41% of all cases are idiopathic anaphylaxis. Since the introduction of new diagnostic methods such as molecular diagnostics (MD) in our centre, the percentage of idiopathic anaphylaxis in the Anaphylaxis Register has significantly decreased. The purpose of this study was to identify possible causes of idiopathic anaphylaxis in patients with a history of moderate to severe anaphylactic reactions. After using MD, the causative agent was found in another 29 people. The proportion of people with idiopathic anaphylaxis in the Registry decreased from 9.2% to 3.5%. There were no significant differences in the incidence, although men appear to be slightly more common in primary idiopathic anaphylaxis. The mean age of primary idiopathic anaphylaxis was 40 years, but this was as high as 51 for anaphylaxis with alpha-gal allergy. Exercise may or may not be present as a cofactor despite its established role, e.g., in wheat-dependent exercise-induced anaphylaxis (WDEIA). In most of the analyzed cases, i.e., 70%, the reaction took place within an hour. The longest time interval from exposure to the development of symptoms is in the case of alpha-gal allergy; in this analysis, it was at least 5 h after ingestion of the so-called "red meat". Patients are not aware of the disease, or further attacks cannot be prevented. As many as 80% had idiopathic anaphylaxis prior to visiting the centre, and 80% developed anaphylaxis after visiting the centre, which emphasizes the need to not stop the medical team in their search for the causes. As many as 93% of cases required medical intervention, of which adrenaline was used only in 34.5%, antihistamines in 86%, systemic glucocorticosteroids (sCS) in 75%, and fluids in 62% of cases. A total of 83% of patients received an emergency kit for self-administration. Idiopathic anaphylaxis can be resolved as known-cause anaphylaxis after a thorough medical history and, if possible, without exposing the patient after using appropriate, modern in vitro diagnostic methods, including molecular diagnostics. The diagnosis of idiopathic anaphylaxis should extend the diagnosis to include alpha-gal syndrome, LTP syndrome and WDEIA.

Is it worth already in the first step exceeding the 3-g protein limit for the oral food challenge for food protein-induced enterocolitis syndrome?

Is it worth already in the first step exceeding the 3-g protein limit for the oral food challenge for food protein-induced enterocolitis syndrome?

Hypoallergenic Wheat Line (1BS-18H) Lacking ω5-Gliadin Induces Oral Tolerance to Wheat Gluten Proteins in a Rat Model of Wheat Allergy.

The early ingestion of food can prevent the onset of food allergy related to inducing oral tolerance (OT). We developed the Hokushin wheat line as a hypoallergenic wheat (1BS-18H) lacking ω5-gliadin, a major allergen of wheat-dependent exercise-induced anaphylaxis (WDEIA). The 1BS-18H wheat had lower ability of sensitization for ω5-gliadin compared with Hokushin wheat. Here, we evaluated the induction of OT to gluten and ω5-gliadin by the early consecutive ingestion of 1BS-18H gluten using a rat model of wheat allergy. Rats were subcutaneously immunized with commercial gluten or native ω5-gliadin following the daily oral administration of gluten. The daily oral administration of 1BS-18H gluten for 5 days before immunization suppressed the increase in gluten- or ω5-gliadin-specific IgE and IgG1 antibodies induced by immunization to a level similar to Hokushin gluten. Intravenous challenge with gluten or ω5-gliadin did not decrease the rectal temperature in rats with OT induced by 1BS-18H or Hokushin gluten, although it was decreased in non-OT rats. In conclusion, the early consecutive ingestion of 1BS-18H wheat before sensitization induced OT to gluten and ω5-gliadin. These findings support the benefit of 1BS-18H wheat to prevent wheat allergy including WDEIA by consecutive ingestion in humans.

Clinical features and outcomes of patients with wheat-dependent exercise-induced anaphylaxis: a retrospective study

BackgroundWheat-dependent exercise-induced anaphylaxis (WDEIA) is a serious and potentially life-threatening form of wheat allergy. Further episodes can only be prevented by avoiding wheat ingestion or avoiding exercise after wheat intake. Anaphylaxis may recur in some patients post-diagnosis. This study aimed to analyze the clinical features and management/outcomes of WDEIA in China.MethodsWe retrospectively analyzed the clinical characteristics, and laboratory testing of 197 patients with WDEIA. After diagnosis, the patients were followed up as outpatients to evaluate dietary/exercise choice and clinical outcomes.ResultsAmong the 197 WDEIA patients (median age, 37 years), 53.8% were male and 28.4% had other allergic disorders. The median duration of anaphylaxis before diagnosis was 16 months. Significant delays in diagnosis (> 1 years) were recorded in 52.7% of the patients, which has not decreased by years (P = 0.064). Exercise (83.8%), alcohol (12.2%), and nonsteroidal anti-inflammatory drugs (7.1%) were the most common cofactors. The most common clinical features were urticaria (100%), loss of consciousness (82.7%), dyspnea (50.8%), and hypotension (47.2%). Of the 197 eligible patients, 155 responded (78.7%), and 124 (80.0%) of which had no anaphylaxis post-diagnosis. A wheat-free diet prevented future anaphylaxis in 91.7% of the patients, followed by the avoidance of wheat combined with exercise (87%) and reduced wheat intake combined with exercise avoidance (80.5%).ConclusionThe diagnosis of WDEIA is frequently delayed. Therefore, when patients present with unexplained anaphylaxis, the possibility of WDEIA should be considered. A wheat-free diet or avoiding wheat combined with exercise or reduced wheat combined with exercise avoidance helps to significantly reduce the onset of future anaphylaxis. However, approximately one-fifth of patients continue to experience anaphylaxis post-diagnosis. Thus, these patients must always carry epinephrine autoinjectors.

Safety of an inactivated COVID-19 vaccine in patients with - wheat-dependent exercise-induced anaphylaxis

Background: Inactivated vaccines against coronavirus disease-2019 (COVID-19) offer an effective public health intervention to mitigate this devastating pandemic. However, little is known about their safety in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). Methods: We recruited 72 WDEIA patients and 730 healthy matched controls who received an inactivated COVID-19 vaccine. Participants were monitored for 4 weeks after each immunization for adverse reactions and completed questionnaires regarding local and systemic reactions at 7 and 28 days after each vaccination. For those who had received the COVID-19 vaccine prior to enrollment, adverse event data were obtained retrospectively. Results: Local and systemic adverse events occurred at similar rates in the WDEIA group and the control group. In both groups, injection-site pain and fatigue were the most common local and systemic reactions, respectively. Compared with healthy controls, more allergic events were reported in the WDEIA group (after dose 1, 0.5% vs. 4.2%, p=0.019; after dose 2, 0% vs. 1.4%, p=0.089). Allergic reactions mainly manifested as rash, urticaria, and edema, which were mild and controllable. No serious allergic events were reported. Conclusions: The adverse event profile of inactivated COVID-19 vaccine did not differ between WDEIA patients and healthy controls. The risk of allergic reactions in patients with WDEIA seems higher, but no anaphylaxis was reported, and the allergic reactions were controllable. Inactivated COVID-19 vaccines appear to be well-tolerated in WDEIA patients, but patients with potential allergy risks should be cautious.

Basophil Activation to Gluten and Non-Gluten Proteins in Wheat-Dependent Exercise-Induced Anaphylaxis.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a cofactor-induced wheat allergy. Gluten proteins, especially ω5-gliadins, are known as major allergens, but partially hydrolyzed wheat proteins (HWPs) also play a role. Our study investigated the link between the molecular composition of gluten or HWP and allergenicity. Saline extracts of gluten (G), gluten with reduced content of ω5-gliadins (G-ω5), slightly treated HWPs (sHWPs), and extensively treated HWPs (eHWPs) were prepared as allergen test solutions and their allergenicity assessed using the skin prick test and basophil activation test (BAT) on twelve patients with WDEIA and ten controls. Complementary sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE), high-performance liquid chromatography (HPLC), and mass spectrometry (MS) analyses revealed that non-gluten proteins, mainly α-amylase/trypsin inhibitors (ATIs), were predominant in the allergen test solutions of G, G-ω5, and sHWPs. Only eHWPs contained gliadins and glutenins as major fraction. All allergen test solutions induced significantly higher %CD63+ basophils/anti-FcεRI ratios in patients compared with controls. BAT using sHWPs yielded 100% sensitivity and 83% specificity at optimal cut-off and may be useful as another tool in WDEIA diagnosis. Our findings indicate that non-gluten proteins carrying yet unidentified allergenic epitopes appear to be relevant in WDEIA. Further research is needed to clarify the role of nutritional ATIs in WDEIA and identify specific mechanisms of immune activation.

Evaluation of Allergenicity on a ω-5 Gliadin-Deficient Cultivar in Wheat-Dependent Exercise-Induced Anaphylaxis

Purposeω-5 gliadin is the major allergen that causes wheat-dependent exercise-induced anaphylaxis (WDEIA). Recently, a missing mutant wheat cultivar at 1B chromosome Glu-B3 and closely linked Gli-B1 loci was bred. This cultivar (ω5D) has a deficiency in ω-5 and γ-gliadins as well as some low-molecular-weight glutenins. We evaluated specific immunoglobulin E (sIgE) reactivity of the ω5D in WDEIA patients compared to wild-type cultivar.MethodsSerum samples from 14 WDEIA and 7 classic wheat allergy patients were used to compare the allergenicity of ω5D and wild-type cultivars using immunoglobulin E immunoblotting, enzyme-linked immunosorbent assay (ELISA), and ImmunoCAP inhibition assays.ResultsImmunoblotting revealed that ω5D extracts had less sIgE binding to gliadins and glutenins in WDEIA sera than wild-type extracts. Immunoblot inhibition assay for gliadin sIgE reactivity also showed that ω5D gliadins had less allergenicity than wild-type gliadins. ELISA inhibition assay showed stronger allergenicity of gliadins than glutenins, although they had cross-reactivity. This assay also showed that the 50% inhibitory concentrations (IC50) of ω5D extracts against gliadin- or glutenin-sIgE reactivity were approximately 4-fold higher in WDEIA patients than those of wild-type extracts. The inhibition capacity of ω5D gliadins against recombinant ω-5 gliadin-sIgE reactivity was also lower in WDEIA patients than that of wild-type.ConclusionsThe allergenicity of the ω5D cultivar is markedly lower for WDEIA patients in the sIgE inhibition tests. These results suggest that the ω5D cultivar may be a safe alternative for WDEIA patients.

Causes and Diagnostic Usefulness of Tryptase Measurements for Anaphylaxis in a Korean Tertiary Care General Hospital.

The causes of anaphylaxis in a general hospital may differ from those occurring in a community setting. Underlying diseases in admitted patients and vague presenting symptoms can make the diagnosis of anaphylaxis difficult. Serum tryptase measurements may provide valuable evidence for diagnosing anaphylaxis in admitted patients. This study was designed as a retrospective study of 53 patients with an anaphylaxis episode at a Korean tertiary care general hospital. Tryptase levels were measured at baseline and different time points from the onset of anaphylaxis. Drugs (42 cases; 79.2%) and foods (10 cases; 18.9%) were the most common causes of anaphylaxis. In drug-induced anaphylaxis, antibiotics (24.5%), anticancer medications, which included monoclonal antibodies (22.6%), and contrast agents (11.3%) were the most frequent causes. The muscle relaxant eperisone (5.7%), neuromuscular blocking agent rocuronium (5.7%), and its antagonist sugammadex (3.8%) were other frequent triggering agents. Wheat-dependent exercise-induced anaphylaxis was the most common entity in food-induced anaphylaxis. Tryptase concentrations were higher in patients with higher grades of anaphylaxis, as well as in accidental anaphylaxis, compared to meticulously provoked anaphylaxis. Overall diagnostic sensitivity was higher for tryptase algorithm criteria (≥[1.2×baseline+2] µg/L: 71.4%) than for abnormal tryptase level criteria (≥11.4 µg/L: 52.8%). The triggers of anaphylaxis in a Korean tertiary care hospital were diverse, including beta-lactam antibiotics, anticancer medications, contrast medias, eperisone, nonsteroidal anti-inflammatory drugs, rocuronium, sugammadex, and wheat. Tryptase measurements provided valuable evidence for diagnosis, and the sensitivity of algorithm criteria was superior to that of the abnormal value criteria.