House Dust Mite Precision Allergy Molecular Diagnosis (PAMD@) in the Th2-prone Atopic Dermatitis Endotype

Abstract

Atopic dermatitis (AD) endotyping might be important for developing personalized diagnostic and therapeutic strategies to the different phenotypes. The current study investigated the IgE molecular profile to Dermatophagoides pteronyssinus (D. pteronyssinus) in a subset of patients afflicted with varying severity stages of atopic dermatitis in a subtropical region subjected to a high perennial house dust mite (HDM) exposure. We selected patients showing a clinically relevant sensitization to HDM with mild-to-moderate and severe AD according to their basal Severity Scoring Atopic Dermatitis (SCORAD) index. Skin prick test (SPT) with standardized mite extracts, as well as a Precision Allergy Molecular Diagnosis (PAMD@) panel including nine different D. pteronyssinus allergens and the related protein allergenic characterization, were assessed in all serum samples. A total of 80 European American AD patients with the marked T2 endotype confirmed their eligibility for the study. Major allergens (Der p 23, Der p 2, and Der p 1) were present in more than 86% of all subjects, with mid-tier allergens (Der p 5, Der p 7, and Der p 21) reaching up to 65%. A serodominant role for Der p 11 could not be quantitatively confirmed in the present cohort. The proposed component resolved diagnosis (CRD) panel appeared to be sufficient to obtain a precise D. pteronyssinus molecular diagnosis in AD patients subjected to a climate-dependent high-mite allergen exposure. The raised seroprevalence of IgE response to Der p 23 confirmed this constituent as a major D. pteronyssinus allergen in severe stages of atopic dermatitis. A clinically driven molecular approach appears to be essential to frame a more precise diagnosis and therapy of this heterogeneous allergic condition.

Keywords: Dermatophagoides pteronyssinus; allergen; allergy; atopic dermatitis; endotype; precision allergy molecular diagnosis.

Figure 1

Quantitative average number of Dermatophagoides pteronyssinus molecules recognized by IgE antibodies in atopic dermatitis patients (n = 80). Median overall values of specific IgE to Der p 1, Der p 2, Der p 5, Der p 7, Der p 21, and Der p 23 showed quantitative significantly (p < 0.05) higher titers in the severe atopic dermatitis subjects. No statistical differences were found in the median overall values of specific IgE to Der p 10, Der p 11, and Der p 20 in all patients, regardless of their Severity Scoring Atopic Dermatitis index. Severe: S; mild–moderate: MM; specific IgE: sIgE. ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Figure 2

Western blot of atopic dermatitis (AD) subjects (n = 80) sensitized to Dermatophagoides pteronyssinus (D. pteronyssinus) according to their basal Severity Scoring Atopic Dermatitis (SCORAD) index (subfigures (A): Mild-Moderate AD and (B): Severe AD). A SCORAD index > 40 was regarded as a marker in the severe forms of AD. Although different repertoires of IgE response to D. pteronyssinus were found, a notably larger amount of additional protein binding was found in those subjects afflicted with severe AD.