Serological, genomic and structural analyses of the major mite allergen Der p 23

Abstract

Background Der p 23 was recently identified in a European population as a major allergen and potentially a chitin binding protein. Objective This study sought to assess the importance of Der p 23 among other Dermatophagoides allergens in a North American population, and to determine the structure for functional characterization. Methods IgE binding to Der p 23, Der p 1, Der p 2, Der p 5, Der p 7, and Der p 8 was measured by ELISA. RNA-seq data from D. pteronyssinus were compared as estimates of allergen expression levels. The structure was analyzed by X-ray crystallography and NMR. Results Despite a high prevalence of Der p 23, (75% versus 87% and 79% for Der p 1 and Der p 2, respectively), the anti-Der p 23 IgE levels were relatively low. The patient response to the 6 allergens tested was variable (n=47), but on average anti-Der p 1 and anti-Der p 2 together accounted for 85% of the specific IgE. In terms of abundance, the RNA expression level of Der p 23 is the lowest of the major allergens, 30-fold less than and 7-fold less than Der p 2. The structure of Der p 23 is a small, globular protein stabilized by two disulfide bonds, which is structurally related to allergens such as Blo t 12 that contain carbohydrate binding domains that bind chitin. Functional assays failed to confirm chitin binding by Der p 23. Conclusions and Clinical Relevance Der p 23 accounts for a small percentage of the IgE response to mite allergens, which is dominated by Der p 1 and Der p 2. The prevalence and amount of specific IgE to Der p 23 and Der p 2 are disproportionately high compared to the expressions of other Dermatophagoides allergens.

Cross-Reactivity between Major IgE Epitopes of Family 5 Allergens from <b><i>Dermatophagoides pteronyssinus</i></b> and <b><i>Blomia tropicalis</i></b>

“…The prevalence of anti-Der p 5 and anti-Blo t 5 IgE in the cohort of sera from the HDM-allergic patients located in the Dellys region, northern Algeria, was 23 and 18% respectively. We also confirmed that the allergens from family 5 are minor allergens (as described in [5]).…”

“…Interestingly, 4 sera (S24, S40, S45, and S58) contained IgE against both tested allergens. Our results showed that D. pteronyssinus and B. tropicalis are involved in the development of HDM allergy [5]. The prevalence of anti-Der p 5 and anti-Blo t 5 IgE in the cohort of sera from the HDM-allergic patients located in the Dellys region, northern Algeria, was 23 and 18% respectively.…”

“…HDM allergens are classified into 33 different groups. Among them, Der p 1 and Der p 2 are two major allergens from D. pteronyssinus with IgE-binding frequencies > 80% [5]. …”

“…Others show that Der p 5 is strongly related to the development of asthma in allergic patients [3, 15, 16] and that significantly higher concentrations of specific IgE (sIgE) to Der p 5 can be observed in asthmatic patients. Furthermore, Der p 5 is secreted in very small quantities, and the number of mite-allergic patients specifically recognizing Der p 5 is disproportionately high considering its low expression level [5]. On the other hand, sensitization to B. tropicalis is strongly associated with allergenic diseases where Blo t 5 is the major allergen [17-19].…”

Allergens of <b><i>Blomia tropicalis</i></b>: An Overview of Recombinant Molecules

“…Its chitin-binding activity was experimentally confirmed by Zakzuk et al [26]. Interestingly, chitin binding has been predicted for Der p 23 and Der p 18, but only a weak binding activity has been demonstrated for Der p 18 [71,72,73]. The Blo t 12 sequence contains a putative signal peptide (amino acid residues 1-20) resulting in a 14-kDa mature protein [70].…”