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

Background: 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. Objectives: We aimed to execute an extensive bibliometric study, focusing on the past 30 years of literature related to wheat allergy. Methods: 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. Results: 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. Conclusion: 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.

Effect of Adding Chestnut Inner Skin on Allergenic Protein, Antioxidant Properties, and Quality of Bread.

Wheat-dependent, exercise-induced anaphylaxis has no fundamental cure and requires patients to refrain from wheat consumption or to rest after eating. Although hypoallergenic wheat production by enzymatic degradation or thioredoxin treatment has been investigated, challenges still exist in terms of labor and efficacy. We investigated a hypoallergenic wheat product manufacturing technology that takes advantage of the property of tannins to bind tightly to proteins. Commercially available bread wheat (BW) and hypoallergenic wheat (1BS-18 "Minaminokaori", 1BS-18M) were used. Chestnut inner skin (CIS) was selected as a tannin material based on the screening of breads with added unused parts of persimmon and chestnut. Hypoallergenicity was evaluated using Western blotting. The effect of CIS addition on the antioxidative properties of bread was also measured. For both BW and 1BS-18M, CIS addition reduced the immunoreactivity of wheat allergens. Antioxidant activities increased with increasing CIS substitution. However, 10% CIS-substituted breads were substantially less puffy. Five percent CIS substitution was optimal for achieving low allergenicity, while maintaining bread quality. The strategy investigated herein can reduce allergies related to wheat bread consumption. In this study, the evaluation of hypoallergenicity was limited to instrumental analysis. In the future, we will evaluate hypoallergenicity through clinical trials in humans.

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.

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

Background: Wheat-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. Methods: We 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. Results: We 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). Conclusion: Clinical 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.

Case report-wheat-dependent exercise-induced anaphylaxis in a patient with chronic spontaneous urticaria: A diagnostic challenge.

Wheat-dependent exercise-induced anaphylaxis is a rare but severe form of anaphylaxis that occurs after consuming wheat products and engaging in physical activity. A case study of a 30-year-old woman suffering from chronic urticaria for the last 5 years highlights the difficulty in diagnosing this condition, as specific triggers were not identified. A diagnostic study called MADx revealed a positive analysis for omega-5-gliadin, leading to a diagnosis of wheat-dependent exercise-induced anaphylaxis. Delayed diagnosis is a common issue, and it can be challenging to distinguish wheat-dependent exercise-induced anaphylaxis from other conditions with similar symptoms. The treatment involves avoiding wheat products and always carrying an epinephrine auto-injector. When evaluating patients with similar symptoms, healthcare providers should include wheat-dependent exercise-induced anaphylaxis in their differential diagnosis. Patients should be educated about the symptoms, triggers, and management to seek immediate medical attention in an emergency.

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/ß-, 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.

Appearance of food-dependent exercise-induced anaphylaxis as an inflammatory disease: a pediatric case report and differential diagnosis.

Anaphylaxis is the most serious of all allergic reactions. Despite advances in the knowledge of anaphylaxis, its clinical manifestations continue to be under-recognized. Indeed, proper diagnosis of anaphylaxis is often missed, and the treatment is delayed. The underlying causes are still under investigation globally. Inflammation represents the cornerstone of pathophysiology of anaphylaxis. Food-dependent exercise-induced anaphylaxis (FDEIA) is a rare clinical manifestation characterized by a chronological sequence in which food ingestion followed by physical exercise leads to anaphylaxis. Its mechanisms are yet to be fully explained. We report the case of a 14-year-old Chinese male who lost consciousness while undergoing physical activity at school. Several differential diagnoses were considered such as hypovolemic shock, septic shock, anaphylactic shock or neurological adverse event. Finally, the diagnosis of FDEIA was made. This case highlights the difficulties in diagnosing FDEIA and its management, especially when the clinical history is not complete and detailed.

Appearance of food-dependent exercise-induced anaphylaxis as an inflammatory disease: a pediatric case report and differential diagnosis

Anaphylaxis is the most serious of all allergic reactions. Despite advances in the knowledge of anaphylaxis, its clinical manifestations continue to be under-recognized. Indeed, proper diagnosis of anaphylaxis is often missed, and the treatment is delayed. The underlying causes are still under investigation globally. Inflammation represents the cornerstone of pathophysiology of anaphylaxis. Food-dependent exercise-induced anaphylaxis (FDEIA) is a rare clinical manifestation characterized by a chronological sequence in which food ingestion followed by physical exercise leads to anaphylaxis. Its mechanisms are yet to be fully explained. We report the case of a 14-year-old Chinese male who lost consciousness while undergoing physical activity at school. Several differential diagnoses were considered such as hypovolemic shock, septic shock, anaphylactic shock or neurological adverse event. Finally, the diagnosis of FDEIA was made. This case highlights the difficulties in diagnosing FDEIA and its management, especially when the clinical history is not complete and detailed (AU)

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.

BACKGROUND: In 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. METHODS: In 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. RESULTS: During 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. CONCLUSIONS: Long-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.

A Case of Tooth Extraction in a Patient with Food-Dependent Exercise Induced Anaphylaxis.

A 29-year-old Japanese man with food-dependent exercise-induced anaphylaxis (FDEIA) underwent tooth extraction under general anesthesia. FDEIA is a rare condition in which anaphylaxis occurs due to exercise load or oral administration of NSAIDs after ingestion of allergens. Wheat is often the cause in FEDIA, defined as wheat-dependent exercise-induced anaphylaxis (WDEIA). It is an allergy that is not well known in the dental field. Patients may ingest the causative food on a regular basis because they do not develop without factors such as exercise. Post extraction period was uneventful as the patient was instructed not to ingest wheat before the treatment or while he was taking NSAIDs. We were able to safely extract teeth without causing 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.

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

BACKGROUND: Wheat-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. METHODS: We 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. RESULTS: Among 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%). CONCLUSION: The 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.

[Dermatitis herpetiformis and other forms of wheat sensitivity]. / Dermatitis herpetiformis und sonstige Formen der Weizensensitivität.

BACKGROUND: Wheat sensitivity is a collective term for several, especially gastrointestinal, diseases that occur as part of a hypersensitivity reaction after wheat consumption. The symptoms, which are mostly similar to those of irritable bowel syndrome, are often accompanied by skin lesions. In addition to celiac disease and dermatitis herpetiformis, the cutaneous manifestation of celiac disease, wheat sensitivity also includes nonceliac gluten sensitivity (NCGS), allergic nickel contact mucositis, wheat allergy, amylase-trypsin inhibitor intolerance, and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) intolerance. OBJECTIVES: This review article aims to provide an overview of the clinical, especially dermatological and gastrointestinal features of the different forms of wheat sensitivity. Diagnosis and therapeutic management are also discussed. MATERIALS AND METHODS: A selective literature search was carried out with evaluation of our own clinical data. RESULTS: The skin lesions in dermatitis herpetiformis are very disease-specific. In contrast, wheat allergy often shares signs and symptoms with many other diseases. Other forms of wheat sensitivity cause primarily gastrointestinal abnormalities, but extra-intestinal manifestations can also occur. Their diagnosis is often complex and requires cross-disciplinary collaboration with experts in gastroenterology. The therapy consists of a wheat- or gluten-free diet. CONCLUSIONS: Knowledge of the different and frequently occurring dermatological signs of wheat sensitivity is of great importance, because dermatological manifestations associated with gastrointestinal pathology, intolerance reactions, and allergies appear more and more frequently.

Clinical Features of Wheat Allergy Are Significantly Different between Tri a 14 Sensitized Patients and Tri a 19 Sensitized Ones.

INTRODUCTION: Wheat is the most important cereal for human nutrition but its high consumption is associated to an increasing complaint of wheat-related disorders, many of which are allergic in nature and different in respect to the involved allergens. In this study, we compared the clinical aspects of wheat allergy presented by patients sensitized to Tri a 19 in respect to those presented by patients sensitized to Tri a 14. METHODS: With this aim, we selected patients sensitized to 1 or both of the 2 allergens, and among these we identified those who were really wheat allergic and reactive on the basis of a standardized methodology. We evaluated the clinical features such as the kind and severity of symptoms, the coexistence of triggering factors such as physical exercise and NSAIDs and alcohol consumption, and the association with other allergens and with various immunologic parameters. Wheat allergy in Tri a 19 sensitized patients was confirmed through a questionnaire while the patients sensitized to Tri a 14 underwent wheat challenge with 100 g of pasta followed by exercise on a treadmill. RESULTS: Seventy-nine patients sensitized to Tri a 14 and 40 patients sensitized to Tri a 19 were recruited. The 2 sensitizations were independent with a significant inverse relation (p < 0.00001). The Tri a 19 sensitized patients presented, in respect to the Tri a 14 sensitized ones, an older age (p = 0.0017), a higher risk to be wheat allergic (p < 0.0001), a higher severity of the reactions (p < 0.00001) and a higher association with some cofactors, namely alcohol (p < 0.0005) and physical exercise (p = 0.003). On the contrary, Tri a 14 sensitization was associated with atopy (p < 0.0001), with a higher probability of patients being asymptomatic (p < 0.0001) and being sensitized to other foods, in particular to nuts and cereals (p < 0.00001). CONCLUSIONS: Sensitization to Tri a 19 or Tri a 14 determines different clinical pictures. In particular, sensitization to Tri a 19 implies a higher probability of severe reactions, even dependent on daily triggers, while that to Tri a 14 implies a higher cross-reactivity with other foods but it's more frequently asymptomatic, making a food challenge necessary to prevent useless food avoidance.

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 (AU)

The basophil activation test differentiates between patients with wheat-dependent exercise-induced anaphylaxis and control subjects using gluten and isolated gluten protein types.

BACKGROUND: Oral food challenge using gluten and cofactors is the gold standard to diagnose wheat-dependent exercise-induced anaphylaxis (WDEIA), but this procedure puts patients at risk of an anaphylactic reaction. Specific IgE to ω5-gliadins as major allergens and skin prick tests to wheat may yield negative results. Thus, we designed a proof-of-principle study to investigate the utility of the basophil activation test (BAT) for WDEIA diagnosis. METHODS: Different gluten protein types (GPT; α-, γ-, ω1,2- and ω5-gliadins, high-molecular-weight glutenin subunits [HMW-GS] and low-molecular-weight glutenin subunits [LMW-GS]) and gluten were used in different concentrations to measure basophil activation in 12 challenge-confirmed WDEIA patients and 10 control subjects. The results were compared to routine allergy diagnostics. Parameters analyzed include the percentage of CD63+ basophils, the ratio of %CD63+ basophils induced by GPT/gluten to %CD63+ basophils induced by anti-FcεRI antibody, area under the dose-response curve and test sensitivity and specificity. RESULTS: GPT and gluten induced strong basophil activation for %CD63+ basophils and for %CD63+/anti-FcɛRI ratio in a dose-dependent manner in patients, but not in controls (p < 0.001, respectively). BAT performance differed from acceptable (0.73 for LMW-GS) to excellent (0.91 for ω5-gliadins) depending on the specific GPT as evaluated by the area under the receiver operating characteristic curve. Patients showed individual sensitization profiles. After determination of the best cut-off points, ω5-gliadins and HMW-GS showed the best discrimination between patients and controls with a sensitivity/specificity of 100/70 and 75/100, respectively. CONCLUSION: This study shows the alternative role of BAT in better defining WDEIA and the causative wheat allergens. The best BAT parameters to distinguish WDEIA patients from controls were %CD63+ basophil values for ω5-gliadins and HMW-GS.

Genome-wide association study reveals an association between the HLA-DPB1∗02:01:02 allele and wheat-dependent exercise-induced anaphylaxis.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a life-threatening food allergy triggered by wheat in combination with the second factor such as exercise. The identification of potential genetic risk factors for this allergy might help high-risk individuals before consuming wheat-containing food. We aimed to identify genetic variants associated with WDEIA. A genome-wide association study was conducted in a discovery set of 77 individuals with WDEIA and 924 control subjects via three genetic models. The associations were confirmed in a replication set of 91 affected individuals and 435 control individuals. Summary statistics from the combined set were analyzed by meta-analysis with a random-effect model. In the discovery set, a locus on chromosome 6, rs9277630, was associated with WDEIA in the dominant model (OR = 3.95 [95% CI, 2.31-6.73], p = 7.87 × 10-8). The HLA-DPB1∗02:01:02 allele displayed the most significant association with WDEIA (OR = 4.51 [95% CI, 2.66-7.63], p = 2.28 × 10-9), as determined via HLA imputation following targeted sequencing. The association of the allele with WDEIA was confirmed in replication samples (OR = 3.82 [95% CI, 2.33-6.26], p = 3.03 × 10-8). A meta-analysis performed in the combined set revealed that the HLA-DPB1∗02:01:02 allele was significantly associated with an increased risk of WDEIA (OR = 4.13 [95% CI, 2.89-5.93], p = 1.06 × 10-14). Individuals carrying the HLA-DPB1∗02:01:02 allele have a significantly increased risk of WDEIA. Further validation of these findings in independent multiethnic cohorts is needed.