Molecular Diagnosis to IgE-mediated Wheat Allergy and Wheat-Dependent Exercise-Induced Anaphylaxis

IgE-mediated wheat allergy is an emerging problem worldwide, particularly prevalent in Northern Europe and parts of Asia. Another unique manifestation of wheat allergy, wheat-dependent exercise-induced anaphylaxis (WDEIA), and hydrolyzed wheat protein-induced urticaria/anaphylaxis/WDEIA, has increasingly been reported in recent decades. Major wheat protein allergens are classified into two main categories: water/salt-soluble proteins (e.g., alpha-amylase inhibitors, lipid transfer proteins (LTP), and avenin-like proteins) and alcohol/diluted acid-soluble proteins (e.g., gliadins and glutenins). The most allergenic wheat proteins responsible for IgE-mediated wheat allergy are gliadins, particularly omega (ω)-5-gliadin, and glutenins. In cases of WDEIA, ω-5-gliadin and LTP have been identified as the major allergens involved. Diagnostic challenges for IgE-mediated wheat allergy and WDEIA exist due to the variable sensitivity and specificity of currently available tests, including skin prick tests (SPT) and serum-specific IgE (sIgE), which may lead to misdiagnosis. These variations in diagnostic value may be attributed to factors such as clinical presentation, the specific allergens involved, the type of SPT extracts used, and the component tested. Additionally, in countries where grass pollen is a primary sensitizer, in vivo or in vitro cross-reactivity between timothy grass and wheat is common. However, this cross-reactivity is usually asymptomatic and lacks clinical significance. Diagnostic methods have been developed to minimize the risks associated with oral food challenge tests (OFC). Novel approaches, including component-resolved diagnostics (CRD), basophil activation tests (BAT), and epitope-specific antibody assays, provide more precise diagnostic options for IgE-mediated wheat allergy, WDEIA, and its subtypes by targeting specific allergens and components. However, further large-scale studies and validations are required to standardize these diagnostic protocols.