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

ABSTRACT:

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.

SUBMITTER: Gabler AM

PROVIDER: S-EPMC8340350 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

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