Victoria Marrugo, J. Alvis Zakzuk, Randy Reina, Karen Donado, Ronald Regino, Isabel Gil, Caterine Meza, Dilia Mercado, Enrique Fernández-Caldas, Leonardo Puerta, Nathalie Acevedo, Luis Caraballo
Introduction Molecular allergy diagnostics for house dust mite (HDM) sensitization includes both allergenic molecules and extracts, but extracts have batch-to-batch variability, incomplete allergen representation and cross-reactivity, which confound results and reduces test accuracy. However, although using extract-free arrays could solve these problems, there is no study that formally supports this change. Therefore, the aim of this study was to compare the diagnostic performance and clinical relevance of measuring specific IgE to Dermatophagoides pteronyssinus and Blomia tropicalis extracts vs. two allergen combinations, Blo t 2/Blo t 5/Blo t 21 and Der p 1/Der p 2/Der p 23. Methods In 201 adults with asthma and matched controls, diagnostic performance of specific IgE towards molecular allergen combinations and extracts were compared using receiver operator characteristics analysis, with physician-diagnosed asthma as reference standard. Associations between specific IgE (extracts and combinations) and type 2 inflammation biomarkers (fractional exhaled nitric oxide and blood eosinophils) were also evaluated. Results Specific IgE frequencies and levels were higher in patients. Allergen combinations and extracts showed equivalent performance. The area under the curve of the combination Blo t 2/Blo t 5/Blo t 21 was similar to that of the B. tropicalis extract: 0.783 and 0.808 respectively ( p = 0.42). Likewise, the area under the curve of the combination Der p 1/Der p 2/Der p 23 was 0.793 and that of extract was 0.788 ( p = 0.8). Notably, IgE response to D. pteronyssinus allergens was more specific than the extract and significantly associated with fractional exhaled nitric oxide and blood eosinophils. Conclusion Our findings provide, for the first time, direct evidence that specific allergen combinations have similar diagnostic performance to HDM extracts in molecular diagnostics, improving test accuracy and supporting a shift toward standardized, molecular-resolved diagnostic strategies. In addition, we found that allergen combinations, and not HDM extracts, are strongly associated with type 2 inflammation biomarkers, supporting their use for personalized asthma management.