Der p 23
Summary
Der p 23 is a novel major allergen of house dust mite (HDM) with reported prevalence among Dermatophagoides pteronyssinus sensitized patients to be 74%. Specific immunoglobulin E (sIgE) to Der p 23 is associated with perennial respiratory symptoms including asthma. Der p 23 exposure in children at school have been reported to be a risk for developing asthma. A high degree of cross-reactivity with Der f 23 is reported, however, the reactivity between Dermatophagoides and Blomia tropicalis is low. Der p 23 demonstrates a high allergenic activity, high frequency of recognition and high levels of IgE-antibodies. It is found on the surface of mite fecal pellets but only in low levels. Therefore reactivity to Der p 23 may be underrepresented in extract-based testing. Due to this property, Der p 23 can be included as an important allergen in a molecular or epitope mixture for specific immunotherapy.
Epidemiology
Worldwide distrubution
Der p 23 is a novel major house dust mite (HDM) allergens. The prevalence of Der p 23 among Dermatophagoides pteronyssinus (Der p) sensitized patients is reported to be 74%. Der p 23 is found to be present on the surface of the fecal particles and in the peritrophic lining of the gut and is strongly correlated with asthma.
Der p 23 adds a value in clarifying the allergic symptoms, especially when reactivity to other Der p components is weak, e.g. in extract-based sIgE tests. According to a study conducted in Germany, 5 out of 97 of HDM-allergic patients were monosensitized to Der p 23 after an evaluation of IgE.
As per a study conducted in Thailand, Der p 23 was more appropriate for HDM allergy component-resolved diagnosis than the HDM extracts. Of 222 Thai HDM-allergic patients tested, 54% of patients displayed Der p 23-specific IgE responses.
According to a study including 217 Portuguese patients with HDM allergy (allergic rhinitis, with or without asthma and a positive skin prick test), 213 patients were sensitized to Der p. However, only 2.8% of 213 patients were monosensitized to Der p 23. The specific IgE (sIgE) level of Der p 23 (12.1 ± 19.9 kUa/L) was demonstrated to be lower than that of Der p 1 (21.7 ± 29.7 kUa/L) and Der p 2 (30.6 ± 34.0 kUa/L). Furthermore, higher levels of sIgE (kUa/L) pertaining to the HDM allergens including, Der p 23 were observed in patients with concurrent rhinitis and asthma when compared with those with rhinitis alone (7.32 vs. 6.65, respectively).
A higher prevalence of asthma with Der p 23 hypersensitivity was observed in HDM-monosensitized patients vs. the non-asthmatics (74% vs. 46%; OR: 3.38; P < 0.0005), as per a study conducted in Italy by Celi et al.
Another study from the literature showed that in 36 European patients with allergic rhinitis, a statistically significant difference in the prevalence of sensitization to Der p 23 was observed in asymptomatic patients (26.3%) vs. patients that were allergic to HDM (70.6%), which was proved by nasal provocation test.
Clinical Relevance
Specific molecules
Der p 23 and contains a chitin-binding domain and demonstrates homology with peritrophin-A domain.
Circular dichroism study demonstrated that Der p 23 comprises of five β-strands (23%) and predominantly random coil elements. The sequence of Der p 23 contains a peritrophin-A domain and a proline, glutamate, serine, and threonine (PEST)-like region. Further, Der p 23 simulates an acidic isoelectric point and illustrates an extended structure caused by the amino acids proline and threonine.
Cross-reactive molecules
A high degree of cross-reactivity is noted between Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts, however, the reactivity between Dermatophagoides and Blomia tropicalis is low. In cases where genuine sensitization is unclear, specific allergen components can be useful to identify primary allergy.
Cross-reactivity of Der p 23 was not observed with Der p 15 and Der p 18 according to a study conducted by Resch et al., with unpublished observations.
Detection methods
According to a study published, the presence of Der p 23 in house dust samples was detected using the ELISA test. Der p 23 was detected in each of the dust samples collected from the mattresses of 18 patients allergic to HDM. The findings demonstrated that the levels of Der p 23 were considerably lower in 88.8% of patients than the Der p 2 levels.
Diagnostics
Disease Severity
Der p 23 is reported to be an important allergen for the diagnosis of HDM allergy, especially when major allergens show a negative result.
AIT Prescription
Der p 23 demonstrates high allergenic activity, high frequency of recognition and high levels of IgE-antibodies. Due to this property, it is suggested that Der p 23 can be included as an important allergen in a molecular or epitope mixture for specific immunotherapy.
Exposure
Based on the theoretical data, it has been implied that there are chances of cross-reactivity between the antibodies against Der p 23 allergens and Dermatophagoides spp.
Prevention And Therapy
Experimental trials
As per a study conducted, Der p 23 content available in the standardized quality (SQ) HDM sublingual immunotherapy (SLIT) tablet was enough to initiate Der p 23-specific IgG4 response in asthmatic patients sensitized to Der p 23 at baseline which showed its significance and immunological relevance. Der p 23 constituted the equivalent of 25.8%-26.1% of Der p 1 in the 3 independent tablet extract of Der p.
However, there was only a marginal increase in the Der p 23 IgE measurements i.e. from 92% to 94% in the HDM-sensitized individuals from the baseline. This did not influence the Der p 23 sensitization status on the clinical effect, therefore, more research is required on Der p 23 pertaining to allergen immunotherapy to demonstrate more clinical relevance.
Cross-Reactivity
The similarity between the amino acid sequence of Der p 23 and Der f 23 (from Dermatophagoides farinae) is reported to be 87%. Different structural studies of Der p 23 and consecutive modeling of Der f 23 on its structure, might imply the occurrence of considerable cross-reactivity between the two proteins.
References
- Eder K, Becker S, Gellrich D, Zieglmayer P, Groger M. The Role of Der p 23 Sensitization: An Analysis of 474 Patients Sensitized to Mite. Int Arch Allergy Immunol. 2020;181(9):689-98.
- Stranzl T, Ipsen H, Christensen LH, Eiwegger T, Johansen N, Lund K, et al. Limited impact of Der p 23 IgE on treatment outcomes in tablet allergy immunotherapy phase III study. Allergy. 2020.
- Matricardi PM. EAACI Molecular Allergology User's Guide. DUST MITE ALLERGY. Part B USING MOLECULAR ALLERGOLOGY IN THE CLINICAL PRACTICE. Chapter B04. Pediatr Allergy Immunol. 2016;27 Suppl 23:105-13.
- Weghofer M, Grote M, Resch Y, Casset A, Kneidinger M, Kopec J, et al. 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. J Immunol. 2013;190(7):3059-67.
- Becker S, Schlederer T, Kramer MF, Haack M, Vrtala S, Resch Y, et al. Real-Life Study for the Diagnosis of House Dust Mite Allergy - The Value of Recombinant Allergen-Based IgE Serology. Int Arch Allergy Immunol. 2016;170(2):132-7.
- Soh WT, Le Mignon M, Suratannon N, Satitsuksanoa P, Chatchatee P, Wongpiyaboron J, et al. The House Dust Mite Major Allergen Der p 23 Displays O-Glycan-Independent IgE Reactivities but No Chitin-Binding Activity. Int Arch Allergy Immunol. 2015;168(3):150-60.
- Limao R, Spinola Santos A, Araujo L, Cosme J, Inacio F, Tomaz E, et al. Molecular Sensitization Profile to Dermatophagoides pteronyssinus Dust Mite in Portugal. J Investig Allergol Clin Immunol. 2020:0.
- Celi G, Brusca I, Scala E, Villalta D, Pastorello E, Farioli L, et al. House dust mite allergy in Italy-Diagnostic and clinical relevance of Der p 23 (and of minor allergens): A real-life, multicenter study. Allergy. 2019;74(9):1787-9.
- Zidarn M, Robic M, Krivec A, Silar M, Resch-Marat Y, Vrtala S, et al. Clinical and immunological differences between asymptomatic HDM-sensitized and HDM-allergic rhinitis patients. Clin Exp Allergy. 2019;49(6):808-18.
- Thomas WR. Hierarchy and molecular properties of house dust mite allergens. Allergol Int. 2015;64(4):304-11.
- Posa D, Hofmaier S, Arasi S, Matricardi PM. Natural Evolution of IgE Responses to Mite Allergens and Relationship to Progression of Allergic Disease: a Review. Curr Allergy Asthma Rep. 2017;17(5):28.
- Mika A, Goh P, Holt DC, Kemp DJ, Fischer K. Scabies mite peritrophins are potential targets of human host innate immunity. PLoS Negl Trop Dis. 2011;5(9):e1331.
- Zhang J, Chen J, Newton GK, Perrior TR, Robinson C. Allergen Delivery Inhibitors: A Rationale for Targeting Sentinel Innate Immune Signaling of Group 1 House Dust Mite Allergens through Structure-Based Protease Inhibitor Design. Mol Pharmacol. 2018;94(3):1007-30.
- Mueller GA, Randall TA, Glesner J, Pedersen LC, Perera L, Edwards LL, et al. Serological, genomic and structural analyses of the major mite allergen Der p 23. Clin Exp Allergy. 2016;46(2):365-76.
- Randall TA, Mullikin JC, Mueller GA. The Draft Genome Assembly of Dermatophagoides pteronyssinus Supports Identification of Novel Allergen Isoforms in Dermatophagoides Species. Int Arch Allergy Immunol. 2018;175(3):136-46.
- WHO/IUIS. Allergen Nomenclature 2019. Available from: http://www.allergen.org/viewallergen.php?aid=296.
- Fanuel S, Tabesh S, Sadroddiny E, Kardar GA. Analysis of predicted B and T-cell epitopes in Der p 23, allergen from Dermatophagoides pteronyssinus. Bioinformation. 2017;13(9):307-12.