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.

Highlights

  • Atopic dermatitis (AD) is a complex inflammatory skin disorder in which an interaction between the genetic predisposition, the skin barrier disruption, an inappropriate immune response, and an abnormal microbial skin colonization contribute to generate a highly heterogeneous clinical phenotype that can be classified according to IgE level [1,2,3].In contrast to intrinsic AD, the extrinsic (80%) phenotype is characterized by high total and environmental serum IgE levels, eosinophilia, personal and family atopic background, and greater rate of filaggrin (FLG) mutation [4,5]

  • More than 90% (72 out 80 subjects) had a former family history of atopy and regarding comorbidities, 71 (88.75%) patients were afflicted with allergic rhinitis and/or asthma, and 8 (10%) had a clinically confirmed food allergy

  • Severity Scoring Atopic Dermatitis (SCORAD) index formula is A/5 + 7B/2 + C, where A is defined as the extent (0–100), B is defined as the intensity (0–18), and C is defined as the subjective symptoms (0–20), with a maximal score of the SCORAD index of 103 [43]

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Summary

Introduction

Atopic dermatitis (AD) is a complex inflammatory skin disorder in which an interaction between the genetic predisposition, the skin barrier disruption, an inappropriate immune response, and an abnormal microbial skin colonization contribute to generate a highly heterogeneous clinical phenotype that can be classified according to IgE level [1,2,3].In contrast to intrinsic AD, the extrinsic (80%) phenotype is characterized by high total and environmental serum IgE levels, eosinophilia, personal and family atopic background, and greater rate of filaggrin (FLG) mutation [4,5]. Considering the fact that AD comprises different disease phenotypes, detailed endotyping based on specific clinical, ethnic, or demographic patient groups has been proposed as a rational approach for characterization and stratification of AD endotypes [10]. The introduction of allergen molecules has had a major effect on analytic specificity and allergy diagnosis. In this regard, precision allergy molecular diagnosis (PAMD@) discriminates cross-reactivity with other allergens from genuine sensitization [11,12], allowing the comprehensive assessment of the patient’s sIgE binding to a panel of individual allergens [13,14]

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