Identification of Der p 23, a Peritrophin-like Protein, as a New Major Dermatophagoides pteronyssinus Allergen Associated with the Peritrophic Matrix of Mite Fecal Pellets

Abstract

The house dust mite (HDM) Dermatophagoides pteronyssinus is one of most important allergen sources and a major elicitor of allergic asthma. We screened a D. pteronyssinus expression cDNA library with IgE Abs from HDM allergic patients. A cDNA coding for a new major allergen was isolated, which showed sequence homology to peritrophins, which contain chitin-binding domains and are part of the peritrophic matrix lining the gut of arthropods. The mature Der p 23 allergen was expressed in Escherichia coli as an 8-kDa protein without its hydrophobic leader sequence and purified to homogeneity. It reacted with IgE Abs from 74% of D. pteronyssinus allergic patients (n = 347) at levels comparable to the two major HDM allergens, Der p 1 and Der p 2. Thus, Der p 23 represents a new major D. pteronyssinus allergen. Furthermore, rDer p 23 exhibited high allergenic activity as demonstrated by upregulation of CD203c expression on basophils from D. pteronyssinus allergic patients. Immunogold electron microscopy localized the allergen in the peritrophic matrix lining the midgut of D. pteronyssinus as well as on the surface of the fecal pellets. Thus, we identified a new major D. pteronyssinus allergen as peritrophin-like protein. The high allergenic activity of Der p 23 and its frequent recognition as respiratory allergen may be explained by the fact that it becomes airborne and respirable through its association with mite feces. Der p 23 may be an essential component for diagnosis and specific immunotherapy of HDM allergy.

The Influence of Chitin on the Immune Response to the House Dust Mite Allergen Blo t 12

“…Both Blo t 12 isoallergens contain a single copy of a CBD (CBM14, PFAM01607) in their C-terminal region, frequently found on proteins that compose the peritrophic matrix of insects and animal chitinases [35,36,37,38]. Sequence similarity between CBM14 and the CBD of each isoallergen was 44%.…”

“…In addition, other replacements that seem to be relevant in the differential binding activity are two proline residues, only present in the second isoform, which are known to influence loop formation. Other HDM allergens such as the peritrophin Der p 23 [37] and the chitinase Der p 15 [42,43] also contain a CBD, but their sequence similarity with Blo t 12 was rather low. This is in agreement with the lack of reactive components to anti-Blo t 12-specific polyclonal and monoclonal antibodies in D. pteronyssinus extracts (Zakzuk et al, unpubl.…”

“…data). Like the other important mite allergens (Der p 1 [16], Der p 2 [44], Blo t 5, Blo t 21 [45] and Der p 23 [37]), Blo t 12 is present in mite feces; this facilitates exposure to the allergen and may explain its frequent IgE recognition by atopic individuals in several tropical populations [20]. …”

Advances in allergen-microarray technology for diagnosis and monitoring of allergy: The MeDALL allergen-chip

“…rDer p 5, rDer p 21 and rDer p 23 were purified as previously described [32][33][34]. Recombinant Der p 7 was purified by hydrophobic interaction chromatography and hydroxyapatite chromatography while the clone 16-derived protein was purified by anion and cation exchange chromatography.…”

Der f 34, a Novel Major House Dust Mite Allergen Belonging to a Highly Conserved Rid/YjgF/YER057c/UK114 Family of Imine Deaminases

“…These allergens have been identified and characterized from mite body, mite feces, or a cDNA library of mite bodies. Der f 1 (cysteine protease), Der f 2 (MD2-like lipid-binding domain protein), and Der f 23 (peritrophin-like protein) are serodominant allergens in D. farinae (7,(15)(16)(17). Serine proteases from D. farinae, including Der f 3 (trypsin), Der f 6 (chymotrypsin), and Der f 9 (collagenase), act on mucosal epithelial cells to induce chemokine production that triggers the migration of inflammatory cells (13, 18 -23).…”