D3.37 - Optimal Single and Combinatorial Diagnostic Approaches for Wheat Allergy in Chinese Children

The gold standard for wheat allergy (WA) diagnosis is oral food challenge, but it is risky, costly and labour-intensive. Skin prick test (SPT) and specific IgE (sIgE) measurement lack sufficient diagnostic accuracy, which may be due to wheat extracts lacking salt-insoluble allergens like gliadin and glutenin. Basophil activation test (BAT) has good diagnostic performance for peanut and sesame allergy, but has limited data for WA. Thus, we aimed to assess SPT, sIgE and BAT performance with component-resolved diagnostics for WA.

Eighty children aged 1-17 with parent-reported immediate wheat allergic reactions were recruited. They underwent SPT with whole wheat extract and three in-house wheat preparations: salt-soluble albumin/globulin, ethanol-soluble gliadin, and acid-soluble glutenin. Plasma sIgE concentrations for whole wheat, gliadin, and ω-5 gliadin were measured by ImmunoCAP. BAT was performed on fresh venous blood using Flow CAST kit for three in-house preparations and ω-5 gliadin. All subjects underwent a double-blind, placebo-controlled food challenge (DBPCFC, cumulative dose of 4950 mg wheat protein) to ascertain WA diagnosis. Statistical analyses included Mann-Whitney U or Fisher exact test, receiver-operating characteristic curves and random forest analysis.

Forty-six subjects were wheat allergic and 34 were tolerant to wheat. Gliadin showed the highest area-under-curve values in our allergen panel for SPT (0.86), sIgE (0.89), and BAT (0.83), while the values for whole wheat were 0.76 in SPT and 0.84 in sIgE. The variable importance value for gliadin in SPT ranked first (22.20), indicating it was the most relevant for discriminating WA, followed by gliadin in sIgE (21.98) and BAT (10.43), and wheat extract in sIgE (9.54) and SPT (-4.07). CoFAR grading for severity of allergic reactions during DBPCFC showed a significant difference for SPT-gliadin and BAT-gliadin between Grades 1 and 3, but not for sIgE-gliadin. For stepwise diagnostic algorithm, SPT followed by sIgE with gliadin had the highest specificity (0.91) and Youden Index (0.76), while SPT followed by BAT with gliadin had the highest sensitivity (0.87) and comparable Youden Index (0.75).

Gliadin is the most useful wheat component for diagnosing WA in Chinese children. BAT using gliadin is a valuable complement to SPT and sIgE in diagnosing childhood WA. (funded by Health and Medical Research Fund, Health Bureau of Hong Kong SAR [reference 10210336])