Diagnosis Of Wheat-dependent Exercise-induced Anaphylaxis Research Articles

Exercise-food challenge test in patients with wheat-dependent exercise-induced anaphylaxis.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe and potentially life-threatening food allergy. Diagnosis of WDEIA is challenging because reactions are not always reproducible. This study aimed to evaluate the positivity rate of exercise-food challenge test at our allergy unit in order to confirm the diagnosis, and to investigate the effect on the episode of reactions after the test. This retrospective evaluation included patients aged 5-60 years who presented at the pediatric and adult allergy units of Siriraj Hospital during 2014-2018 with a convincing history of WDEIA and who underwent a 4-day exercise-food challenge test. Demographic data, challenge test result, and episodes of the reaction before and after the challenge test were obtained. Fourteen of the 17 patients that were enrolled were included in the analysis. The 3 excluded patients were found to have IgE-mediated wheat allergy. Median age and time to diagnosis was 18.3 years (range: 10.5-43.4) and 1.8 years (range: 0.3-6.2). History of recurrent acute urticaria before the onset of anaphylaxis was reported in 5 patients (35.7%). Exercise-food challenge test was positive in 10 patients (71.4%). Median mean number of exacerbations per year before and after the confirmation test was 2 (range: 1-10) and 1 (range: 0-3), respectively. For WDEIA, time to diagnosis was delayed, and one-third of patients had recurrent acute urticaria proceeding anaphylaxis onset. Our exercise-food challenge test could be utilized safely in both children and adult and able to elicit symptoms in two-third of patients.

Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis

Oral wheat plus cofactors challenge tests in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) produce unreliable results. We sought to confirm WDEIA diagnosis by using oral gluten flour plus cofactors challenge, to determine the amount of gluten required to elicit symptoms, and to correlate these results with plasma gliadin levels, gastrointestinal permeability, and allergologic parameters. Sixteen of 34 patients with a history of WDEIA and ω5-gliadin IgE underwent prospective oral challenge tests with gluten with or without cofactors until objective symptoms developed. Gluten reaction threshold levels, plasma gliadin concentrations, gastrointestinal permeability, sensitivities and specificities for skin prick tests, and specific IgE levels were ascertained in patients and 38 control subjects. In 16 of 16 patients (8 female and 8 male patients; age, 23-76 years), WDEIA was confirmed by challenges with gluten alone (n= 4) or gluten plus cofactors (n= 12), including 4 patients with previous negative wheat challenge results. Higher gluten doses or acetylsalicylic acid (ASA) plus alcohol instead of physical exercise were cofactors in 2 retested patients. The cofactors ASA plus alcohol and exercise increased plasma gliadin levels (P< .03). Positive challenge results developed after a variable period of time at peak or when the plateau plasma gliadin level was attained. Positive plasma gliadin threshold levels differed by greater than 100-fold and ranged from 15 to 2111 pg/mL (median, 628 pg/mL). The clinical history, IgE gliadin level, and baseline gastrointestinal level were not predictive of the outcomes of the challenge tests. The challenge-confirmed sensitivity and specificity of gluten skin prick tests was 100% and 96%, respectively. Oral challenge with gluten alone or along with ASA and alcohol is a sensitive and specific test for the diagnosis of WDEIA. Exercise is not an essential trigger for the onset of symptoms in patients with WDEIA.

Serum Gliadin Monitoring Extracts Patients with False Negative Results in Challenge Tests for the Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis

Challenge testing with wheat plus exercise and/or aspirin is a gold standard for the diagnosis of wheat-dependent exercise-induced anaphylaxis (WDEIA); however, the test may often yield false-negative results. Our previous study suggested that an increase in serum wheat gliadin levels is required to induce allergic symptoms in patients with WDEIA. Based on this knowledge, we sought to extract the patients with false negative results in the challenge tests of WDEIA. Thirty-six patients with suspected WDEIA were enrolled. First, group categorizations-Group I, challenge tests were positive; Group II, challenge tests were negative and serum gliadin were undetectable; Group III, challenge tests were negative and serum gliadin were detectable-were given according to the results of wheat plus exercise and/or aspirin challenge testing and serum gliadin levels. Second, diagnoses were made using retests and/or dietary management in Group II and III. Positive results for wheat plus exercise and/or aspirin challenge tests gave a diagnosis of definite WDEIA in 17 of 36 patients (Group I). Of the remaining 19 challenge negative patients, serum gliadin was undetectable in ten patients (Group II). Of the ten patients (Group II), three of them were diagnosed as definite WDEIA by retesting and six of them were diagnosed as probable WDEIA using a wheat elimination diet, whereas one patient was non-WDEIA. In the rest of the nine challenge negative patients, serum gliadin was detectable (Group III). No allergic episodes with a normal diet provided a diagnosis of non-WDEIA in seven of the nine patients, whereas the remaining two patients were probable WDEIA or had another food allergy because of repeated episodes. Our study revealed that serum gliadin monitoring during challenge testing is useful.

IgE detection to α/β/γ‐gliadin and its clinical relevance in wheat‐dependent exercise‐induced anaphylaxis

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is characterized by anaphylactic reactions after wheat ingestion and physical exercise. IgE antibodies to recombinant ω(5) -gliadin are detectable in a majority of WDEIA patients, but other wheat allergens may also play a role in elicitation of WDEIA. Here, we performed a comprehensive analysis of IgE reactivity to different wheat proteins in 17 patients with confirmed WDEIA by ImmunoCAP research prototypes and a semi-quantitative microarray immunoassay with α/β/γ-gliadin, high-molecular-weight (HMW) glutenin, alpha-amylase inhibitor (AAI) dimer, and wheat lipid transfer protein (LTP). By ImmunoCAP, IgE to recombinant ω(5) -gliadin was detectable in 14/17 patients (82%), to α/β/γ-gliadin in 82% including the three patients lacking IgE to ω(5) -gliadin, and to HMW glutenin in 59%. The microarray revealed specifically γ-gliadin as the second most important allergen. These results demonstrate the additional diagnostic value of α/β- and γ-gliadin in particular in ω(5) -gliadin-negative patients in the diagnosis of WDEIA.

Microarray-based detection of specific IgE against recombinant ω-5-gliadin in suspected wheat-dependent exercise-induced anaphylaxis

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a rare IgE-mediated food allergy. Component-resolved measurement of specific IgE (sIgE) against ω-5-gliadin by fluorescence enzyme immunoassay (FEIA) has been postulated as a good predictive decision criterion in the diagnosis of WDEIA. More recently, microarray technology has been introduced into component-resolved diagnostics. The aim of this study was to evaluate the performance of an allergen microarray in the detection of sIgE against ω-5-gliadin in 10 patients with suspected WDEIA and high levels of sIgE against ω-5-gliadin (mean: 9.31±7.53 kU/L, range: 4.24-25.8) as measured by FEIA. Using an old version of the microarray assay (ImmunoCAP ISAC™, Phadia), sIgE against ω-5-gliadin was detected in only 3 of the first 6 patients. The same samples and those of another 4 patients were then analysed with an improved version of the microarray system, yielding elevated levels of sIgE against ω-5-gliadin in all patients. In conclusion, the old version of the microarray was not reliable for the detection of sIgE against ω-5-gliadin in the examined individuals with suspected WDEIA. In contrast, the improved version of the microarray seems to be as adequate as FEIA in the detection of sIgE against ω-5-gliadin. However, further large-scale studies are warranted to confirm these results.

CD203c expression–based basophil activation test for diagnosis of wheat-dependent exercise-induced anaphylaxis

CD203c expression–based basophil activation test for diagnosis of wheat-dependent exercise-induced anaphylaxis

Specific IgE Determination to Epitope Peptides of ω-5 Gliadin and High Molecular Weight Glutenin Subunit Is a Useful Tool for Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis

Wheat omega-5 gliadin and a high m.w. glutenin subunit (HMW-glutenin) have been reported as major allergens in wheat-dependent exercise-induced anaphylaxis. A simultaneous detection of specific IgE to epitope sequences of both proteins is considered to be a reliable method for diagnosis of wheat-dependent exercise-induced anaphylaxis. However, the IgE-binding epitope of HMW-glutenin remains unknown. The aim of this study was to determine the IgE-binding epitopes of HMW-glutenin to establish a useful system of identifying patients with wheat-dependent exercise-induced anaphylaxis. For determination of IgE-binding epitopes of HMW-glutenin overlapping peptides were synthesized and reactivities of IgE Abs in the sera of patients to those peptides were analyzed. Three IgE-binding epitopes, QQPGQ, QQPGQGQQ, and QQSGQGQ, were identified within primary sequence of HMW-glutenin. Epitope peptides, which include IgE-binding sequences of omega-5 gliadin and a HMW-glutenin, were synthesized and peptide-specific IgE Abs were measured by CAP-System fluorescent enzyme immunoassay. Twenty-nine of 30 patients with wheat-dependent exercise-induced anaphylaxis had specific IgE Abs to these epitope peptides. None of the 25 sera from healthy subjects reacted to both epitope peptides. Twenty-five patients with atopic dermatitis who had specific IgE to wheat and/or gluten had very low or nonexistent levels of epitope peptide-specific IgE Abs. These results indicated that measurement of IgE levels specific to epitope peptides of omega-5 gliadin and HMW-glutenin is useful as an in vitro diagnostic method for the assessment of patients with wheat-dependent exercise-induced anaphylaxis.