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

• Published in: Clinical and translational allergy Vol. 11; no. 6; pp. e12050 - n/a
• Main Authors: Gabler, Angelika Miriam, Gebhard, Julia, Eberlein, Bernadette, Biedermann, Tilo, Scherf, Katharina Anne, Brockow, Knut
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2021; John Wiley and Sons Inc; Wiley
• Subjects: Allergens; Allergies; Anaphylaxis; Asthma; basophil activation test; Body mass index; Dermatitis; Disease; Drug dosages; Exercise; Flour; Food allergies; Gluten; Immunoglobulins; Lipids; Proteins; Reagents; Wheat; wheat allergy; wheat‐dependent exercise‐induced anaphylaxis (WDEIA); ω5‐gliadin; gluten; ω5‐gliadin; basophil activation test; wheat‐dependent exercise‐induced anaphylaxis (WDEIA); wheat allergy
• ISSN: 2045-7022; 2045-7022
• DOI: 10.1002/clt2.12050

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.