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House dust mite (HDM) allergens are a diverse group of proteins derived from the fecal pellets and exoskeletons of mites, primarily Dermatophagoides pteronyssinus and Dermatophagoides farinae. These allergens are the most common triggers of perennial allergic diseases, including allergic rhinitis and asthma, affecting a significant portion of the global population [2, 15]. Major allergens such as Der p 1 and Der p 2 possess distinct molecular properties; for instance, Der p 1 is a cysteine protease that facilitates its own entry into the body by degrading epithelial tight junctions, while Der p 2 mimics MD-2 to activate the TLR4 innate immune pathway [9, 14]. In therapeutic practice, HDM allergens serve as the essential components for allergen-specific immunotherapy (AIT), where controlled exposure is used to re-educate the immune system toward tolerance [1, 10]. Modern drug development also explores the use of small-molecule inhibitors to block the enzymatic activity of specific allergens, such as Der p 1, to prevent the initiation of the allergic inflammatory cascade [9].
House dust mite allergens are primarily utilized in allergen-specific immunotherapy (AIT), which induces immune tolerance through the activation of regulatory T (Treg) and B (Breg) cells, the secretion of anti-inflammatory cytokines like IL-10 and TGF-beta, and the shifting of the immune response from a Th2-mediated profile to a Th1/Treg profile [1, 3, 5]. This process results in an isotype switch from allergen-specific IgE to protective IgG4 antibodies, which block allergen-IgE binding [2, 10]. Experimental 'allergen delivery inhibitors' (ADIs) target the cysteine protease activity of allergens like Der p 1 to prevent the disruption of airway epithelial barriers and subsequent innate immune activation [9].
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