Selection of house dust mite–allergic patients by molecular diagnosis may enhance success of specific immunotherapy

• Published in: Journal of allergy and clinical immunology Vol. 143; no. 3; pp. 1248 - 1252.e12
• Main Authors: Chen, Kuan-Wei, Zieglmayer, Petra, Zieglmayer, René, Lemell, Patrick, Horak, Friedrich, Bunu, Carmen Panaitescu, Valenta, Rudolf, Vrtala, Susanne
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2019; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Allergens; Allergens - immunology; Allergies; Animals; Antigens, Dermatophagoides - immunology; Arthropod Proteins - immunology; Asthma; Atopic dermatitis; Clinical trials; Der f 1 antigen; Der f 2 antigen; Der p 1 antigen; Dermatitis; Dermatophagoides pteronyssinus - immunology; Desensitization, Immunologic; Double-Blind Method; Female; Forearm; Glycerol; Histamine; Humans; Hypersensitivity - diagnosis; Hypersensitivity - immunology; Hypersensitivity - therapy; Immunogenicity; Immunoglobulin E; Immunoglobulin E - immunology; Immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulins; Immunotherapy; Male; Middle Aged; Patients; Rhinoconjunctivitis; Young Adult
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2018.10.048

To the Editor: House dust mites (HDMs) are one of the most potent and frequent allergen sources worldwide.1 More than 40% of patients with allergy are sensitized to HDM allergens and suffer from allergic symptoms such as rhinoconjunctivitis, atopic dermatitis, and allergic asthma, the most severe form of respiratory allergy.2 The HDM Dermatophagoides pteronyssinus contains several different allergens of which Der p 1, Der p 2, Der p 5, Der p 7, Der p 21, and Der p 23 are the clinically most relevant allergens according to the frequency of IgE sensitization and the ability to induce allergic reactions.3 Allergen-specific immunotherapy (AIT) is effective and safe for the treatment of HDM allergy,4 but it has been shown that HDM extracts vary regarding the contents of important HDM allergens and extracts used for AIT are standardized only for Der p 1 and Der p 2 according to the guidelines of the European Medicines Agency.5,6 Here, we performed a post hoc analysis of sera from HDM-allergic patients who had been treated by subcutaneous HDM AIT in a double-blind, placebo-controlled clinical study (see Fig E1 in this article's Online Repository at www.jacionline.org), regarding their IgE and IgG reactivity against a comprehensive panel of HDM allergens by ImmunoCAP ISAC technology. [...]it has been shown that HDM allergen extracts mainly contain Der p 2 and Der p 1, whereas other HDM allergens are poorly represented in the allergen extracts.5 It is also possible that mainly Der p 2 and Der p 1 were immunogenic, whereas the other allergen molecules in the allergen extract exhibited poor immunogenicity and hence did not induce IgG responses as has been shown for grass pollen allergen extracts.7 The strong induction of Der p 2–specific IgG antibodies in the active group was associated with a significant decrease in IgE binding to Der p 2 in the chip measurements. First positive control (0.1% histamine solution), second positive control (1% histamine solution), HDM extract in rising concentrations (10, 100, 1,000, 10,000 AU/mL), negative control (glycerol phosphate buffer solution) (Haarlems Allergen Laboratories), and on the right forearm in the reverse order starting with the negative control. The concentration of 10,000 AU/mL was chosen because it was located in the increasing slope of sensitivity for all subjects.Determination of allergen-specific IgE and IgG by microarray technology IgE and IgG reactivity of sera from all subjects (n = 100) and the 3 time points (baseline = week 0, weeks 23 and 47) to a panel of 176 microarrayed allergens including 15 HDM allergens (ie, Der p 1, Der f 1, Der p 2, Der f 2, Der p 4, Der p 5, Der p 7, Der p 10, Der p 11, Der p 14, Der p 15, Der p 18, Der p 21, Der p 23, and clone 16–derived allergen) was determined using a customized version of the ImmunoCAP ISAC microarray (MedALL allergen-chip) (Thermo Fisher Scientific, Uppsala, Sweden) as described.E3 Levels of allergen-specific IgE and IgG antibodies were reported in ISUs with a cutoff of 0.3 ISU.