Table of Contents

d203 Der p 2 Scientific Information Summary Epidemiology Environmental Characteristics Clinical Relevance Prevention and Therapy Molecular Aspects Diagnostic Relevance Compiled By

Component

d203 Der p 2

d203 Der p 2 Scientific Information

Type:

Component

Name; WHO/IUIS:

Der p 2

Biological function:

Group 2 (NPC2 protein family /epidermal secretory proteins)

Allergen code:

d203

Molecular Weight:

15 kDa

Route of Exposure:

Inhalation

Source Material:

Obtained from the digestive tract and is concentrated in the faecal pellets of Dermatophagoides pteronyssinus or recombinant

Summary

Der p 2 is one of the major allergens of house dust mite (HDM) with a reported prevalence among Dermatophagoides pteronyssinus sensitized patients to be between 80-100%. The exposure of Der p 2 is a risk factor for patients with allergic symptoms in multiple organs. IgE Der p 2 is found to be highly predictive of allergen-induced immediate asthmatic response. A high degree of cross-reactivity with Der f 2 (from Dermatophagoides farinae, Der f) is reported. The group 2 allergens are reported to be cross-reactive with storage mites and Blo t 2. The standardized quality HDM sublingual immunotherapy tablet has demonstrated its superiority in improving the symptoms in patients with allergic rhinitis and asthma outcomes. Allergen-specific immunotherapy can be initiated after determining the Der p 2 levels.

Epidemiology

Worldwide distribution

Der p 2 is one of the major allergens of house dust mite (HDM) (1). The prevalence of Der p 2 among Dermatophagoides pteronyssinus sensitized patients is reported to be between 80-100%. Der p 2 is present in the mite fecal particles and is strongly associated with asthma (1-3).

Environmental Characteristics

Source and tissue

Der p 2 is produced as a recombinant protein. Historically, Der p 2 was reported to be obtained from the digestive tract, whereas it is concentrated in the fecal pellets of Dermatophagoides pteronyssinus (4). The mite fecal pellets are found to be around 15-35 µm in diameter (5).

Risk factors

According to a study conducted, sensitization of Der p 2 was more prevalent in adults and further showed its dominance in patients after prolonged disease duration. Der p 2 was reported to be a risk factor for individuals having allergic symptoms due to a higher level of IgE titers against Dermatophagoides pteronyssinus (6).

Detection methods

In a study conducted by Tsai et al, the concentration of Der p 2 was measured using the Der p 2 ELISA kit. On analysis, 25.53 mg of Der p 2 was obtained from one gram of crude Der p 2 extract. The better association was noted between Der p 2 concentration and mite numbers. This approach of Der p 2 detection to control the mite infestation can be useful for allergic patients to prevent the disease (7).

Clinical Relevance

Specific molecules

The Der p 2 allergen comprises of a single domain β-sandwich protein along with six anti-parallel β-strands which are stabilized by three disulfide bonds. Two distinct elongated fragments of high electron density within its hydrophobic cavity are observed in the crystal structure of Der p 2, which further correlates to aliphatic chains of 14–16 carbon atoms (1).

Der p 2 is reported to mimic the molecule of MD-2 (a lipopolysaccharide coreceptor for Toll-like receptor 4) which helps in interacting with the innate immune system. Der p 2 acts as a superior recipient of an immunological signal due to its unique molecular representation. Further, it also helps in conveying the immunologic signals in the current allergic conditions (6).

Cross-reactive molecules

A high degree of cross-reactivity between Der p 2 and Der f 2 (from Dermatophagoides farinae) was found (8). Limited cross-reactivity was noted between the 3 allergens group 2 allergens (Gly d 2, Lep d 2, and Tyr p 2) and Der p 2 (9).

Prevention and Therapy

Experimental trials

According to a meta-analysis of the five trials, major allergens including Der p 2 are responsible to sensitize a high percentage of HDM patients with allergy. The standardized quality (SQ) HDM sublingual immunotherapy (SLIT) tablet was reported to be superior in improving the symptoms in patients with allergic rhinitis and asthma outcomes. Furthermore, proving its effectiveness for a wide range of patients, due to the presence of a 1:1 ratio of the two major HDM allergens (10).

Molecular Aspects

Biochemistry

Der p 2 of HDM has a molecular weight of 15 kDa (11).

Der p 2 complicates the respiratory airway disorder by the initiation of inflammatory cytokines and increasing the cellular component of the intercellular adhesion molecule 1. According to a study conducted, Der p 2 is reported to decrease the viability of BEAS-2B cell after triggering apoptosis. This property of Der p 2 thus triggers the immune responses and damages the airway epithelium. Also, increased intracellular reactive oxygen species (ROS) is another factor through which Der p 2 is reported to increase the airway hyperreactivity. A study by Lin et al reported, intracellular ROS level was promoted by Der p 2, which in turn lead to elevation of Bax/Bcl-2 ratio and release of the cytochrome c in BEAS-2B cell (12).

Isoforms, epitopes, antibodies

A range of isoallergens of Der p 2 are reported from Der p 2.0101 to Der p 2.0115 (13).

In a study, the IgE binding of 21-single site-directed alanine mutants of Der p 2 was tested which were obtained from the serum of dust-mite allergic individuals. The study included a total of 116 dust-mite positive individuals. In these individuals 5 mutants of Der p 2 viz. N10A, E25A, K77A, E102A and K96A demonstrated a consistent decrease in IgE binding across all sensitization groups, and thus comprise the major conformational IgE epitopes of Der p 2 (14).

As per a study performed, the Der p 2.0101 isoform was confirmed to be the most prevalent isoform in HDM extracts. The isoform was formed as a secreted molecule in P. pastoris or refolded from E. coli. A natural-like disulfide bridge distribution and the secondary structure were demonstrated by the yeast-expressed Der p 2 molecule. However, little heterogeneity in cysteine bonds and lower stability was shown by E. coli-derived Der p (15).

A study conducted in the dust mite allergic individuals revealed that 78% of the individuals had Der p 2-specifc IgE. A total of 34 patients demonstrated IgE binding to hNPC2, and 33/34 individuals showed IgE binding to another structurally similar allergen (Der p 2 alone, or both Der p 2 and Blo t 2). The patients’ specific-IgE responses to Der p 2 and hNPC2, and between Der p 2 and Blo t 2 were found to have low to moderate similarities (14).

Cross-reactivity

The group 2 allergens of Dermatophagoides pteronyssinus are the main allergens responsible for the cross-reactivity between storage mites (Tyrophagus putrescentiae) and house dust mites (16). Blo t 2 (allergen of storage mite (Blomia tropicalis)) is reported to have unique IgE epitopes due to which a limited cross-reactivity with Der p 2 has been reported (17).

Diagnostic Relevance

Disease Severity

Evaluation of HDM allergy can be driven by measuring the IgE levels to Der p 2 which a useful diagnostic tool. A study conducted by Minami et al., including 55 DP-sensitized asthmatic patients demonstrated 86% positivity for IgE antibodies to Der p 2. The area under the receiver operating characteristic curves (AUC) for IgE was found as a predictor of immediate asthmatic response (IAR) with a value of 0.906. Furthermore, the specificity of IgE to Der p 2 was higher than IgE to crude DP. IgE Der p 2 was highly predictive of allergen-induced IAR (18).

Der p 2 allergen plays an important role in the human IgE response against HDM. According to a study conducted in Portuguese patients, a significantly high association between serum eosinophil levels and total IgE levels against Der p 2 was noted. The significant predictive ability is observed by the wheal size and eosinophil levels to separate positive Der p 2 levels from negative levels. This displayed the specificity and sensibility wherein; 4.5 mm of wheal size demonstrated a sensibility of 80.5% and a specificity of 50%. Moreover, 5.55% eosinophils demonstrated a sensibility of 49.8% and a specificity of 82.6% (19).

AIT Prescription

A retrospective study was conducted in 279 children with asthma and/or rhinitis. A higher positivity i.e., 71.3% of Der p 2 was noted as compared with Der p 1 (30%). Further, it demonstrated that 76.3% of Der p-positive patients were sensitized to Der p 2. Allergen-specific immunotherapy can be initiated after determining the Der p 2 levels (19).

According to a study performed in-vivo, administration of sublingual immunotherapy of recombinant Der p in Escherichia coli (Der p 2ec) or recombinant Der p in Pichia pastoris (Der p 2pp) was successful in desensitizing the native Der p 2-allergic population thus, efficiently reducing airway hyperresponsiveness as well as allergen-specific Th2 responses (15).

Exposure

The exposure is through inhalation of the mite fecal pellets. Der p 2 is reported to trigger the respiratory epithelial cells, which in turn can intensify the respiratory airway disease by adjuvant-like activation of the lung epithelium, along with its immunogenic properties (20).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Christian Fischer

Last reviewed: October 2020

References

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