Underestimation of House Dust Mite–Specific IgE With Extract-Based ImmunoCAPs Compared With Molecular ImmunoCAPs

Abstract

To identify the most important house dust mite (HDM) allergens using component-resolved diagnostics (CRD).Patients with HDM allergy (n = 53), including 26 who were challenged in an environmental control chamber and 27 who were not challenged.Testing for serum-specific immunoglobulin E (IgE) to 13 HDM proteins was confirmed by ImmunoCAP Immuno Solid-phase Allergen Chip assays (henceforth referred to as CAP-molecular). Only the 6 proteins to which serum-specific IgE was most prevalent were included in further analysis (Der p 1, 2, 5, 7, 21, and 23), and all patients were sensitized to all 6 HDM allergens. An ImmunoCAP assay containing the 6 HDM allergens was prepared (CAP-allergen) and compared with the commercial extract-based ImmunoCAP assay (CAP-extract) and CAP-molecular. The 2 groups were studied in combination and independently.Specific IgE levels by CAP-extract, CAP-allergen, and CAP-molecular correlated with each other, with the best correlation between CAP-extract and CAP-allergen. CAP-allergen levels were higher than CAP-extract levels in 39 out of 53 (70%) patients and significantly higher overall (P < .0001). However, when allergen-specific IgE levels to the 6 predominant allergens were compared in patients with a CAP-extract level greater or less than 20 kU/L, the CAP-molecular levels were only higher in the group with higher CAP-extract levels, indicating that important allergens might be underrepresented in the commercially available CAP-extract assay (especially Der p 2, 5, 21, and 23). In unpublished data, the authors report that higher CAP-extract levels do not correlate with specific manifestations of HDM allergy, but threshold levels for clinical allergy might be established. There was no significant difference in outcomes between the groups.Replacing CAP-extract assays with highly reproducible CAP-molecular assays or by adding recombinant HDM allergens to HDM extracts might improve differentiation of HDM sensitization from HDM allergy.The easy availability and inaccurate interpretation of in vitro tests for serum-specific IgE may overestimate the prevalence of specific allergies. Practitioners must differentiate between sensitization (a positive test result) and allergy (a positive test result and clinical reactivity). We have entered the era of CRD in which we can measure serum-specific IgE levels to some individual proteins, not just to crude extracts of an allergen. We understand that depending on the food and the individual proteins to which a patient makes specific IgE, we gain knowledge as to the likelihood of him or her tolerating a baked product if not the food per se (eg, milk or egg) or of his or her risk for oropharyngeal versus systemic symptoms (eg, peanut and certain tree nuts). Furthermore, we know that the greater diversity of epitopes to which a person makes specific IgE, the greater the likelihood he or she is to be allergic and, in the case of food allergies, the lesser the likelihood he or she will outgrow the allergy. I anticipate that we will eventually have many more assays for specific allergens, improving our diagnostic specificity and sensitivity. It is important to fully understand the interpretation of tests for specific IgE, especially as CRD evolves.