Thaumatin-Like Proteins in Molecular Allergy Diagnostics: Uncommon, Co-Sensitized, and Clinically Inconspicuous? Insights From an Italian Cohort.

Abstract

Thaumatin-like proteins (TLPs) are conserved plant pathogenesis-related proteins with IgE-binding capacity, but their clinical relevance remains poorly defined. Unlike well-characterized panallergens, TLPs are underrepresented in diagnostic panels, and their role in food allergy is largely unexplored. To assess the prevalence, quantitative IgE levels, co-sensitization patterns, and clinical significance of IgE reactivity to two TLPs-Act d 2 (kiwi) and Mal d 2 (apple)-in a large Italian allergic cohort. We conducted a cross-sectional study of 7176 consecutive patients referred to Italian tertiary allergy centers. Specific IgE to TLPs and other plant allergens was measured using ALEX². Clinical outcomes were evaluated, and associations with IgE levels and co-sensitizations were examined using multivariate models. ROC analyses were applied to evaluate the discriminatory ability of Act d 2 IgE for clinical severity. TLP sensitization occurred in 137 patients (1.9%), predominantly to Act d 2. Isolated TLP sensitization was rare (n = 20) and associated with low IgE levels (mean 0.61 ± 0.98 kUA/L) and minimal symptoms. Co-sensitized patients (n = 117) had higher and more variable IgE levels (mean 1.41 ± 3.49 kUA/L) and experienced more clinically relevant reactions, including oral allergy syndrome and food-dependent exercise-induced anaphylaxis. ROC analyses indicated limited discriminatory power of Act d 2 IgE for predicting reaction severity (AUC 0.51-0.61). Multivariate adjustment confirmed no independent association between TLP-specific IgE and moderate or severe symptoms. TLP sensitization is uncommon and generally clinically silent when isolated. Co-sensitization with other panallergens appears to drive allergic manifestations. Quantitative TLP-specific IgE alone provides limited predictive value, emphasizing the importance of integrating molecular diagnostics with clinical phenotyping in precision allergy management.