Omega-5-gliadin-specific immunoglobulin E-positive, but wheat-specific immunoglobulin E-negative wheat allergy dependent on augmentation factors—a frequent presentation

Abstract

Aim: Most patients with wheat allergy dependent on augmentation factors (WALDA) show specific immunoglobulin E (sIgE) to ω5-gliadin. However, some WALDA patients may show negative results when testing for sIgE to total wheat extract. This is the first study to investigate potential clinical and serological differences in patients with ω5-gliadin-positive, challenge-confirmed WALDA dependent on their sensitization to total wheat extract. Methods: Clinical and serological characteristics of patients with challenge-confirmed, ω5-gliadin-positive WALDA were analyzed based on the absence or presence of sIgE to wheat (cut-off 0.35 kUA/L). Results: Thirty-six patients with challenge-confirmed WALDA were included (19 female; median age 50.5 years; median sIgE to ω5-gliadin 6.5 kUA/L). SIgE levels to grass pollen were related to the presence of any atopic comorbidity (P < 0.001) and showed a correlation with sIgE to wheat (P = 0.003), but not to the gluten-related allergens [all not significant (ns)]. Thirty-nine percent of patients (n = 14) showed sIgE levels to wheat lower than 0.35 kUA/L; in 19.4% (n = 7) levels were even below the detection limit of 0.01 kUA/L. WALDA patients without sIgE to wheat showed lower levels of total immunoglobulin E (IgE) and sIgE to wheat gluten, gliadins, and ω5-gliadin (all P < 0.001) as well as to grass pollen (P = 0.03). No significant differences in clinical characteristics like delay until diagnosis, the presence of an atopic condition, reaction severity, or threshold in the oral challenge test were observed. Conclusions: SIgE to wheat extract was associated not only with sensitization against gluten allergens but also reflected total IgE production and concomitant grass pollen allergy, making it an insensitive and unspecific biomarker for WALDA. There were no clinical divergences between WALDA patients without or with sIgE to wheat. SIgE to total wheat extract does not appear to be clinically relevant and remains negative in a significant proportion of WALDA patients.