Table of Contents

d202 Der p 1 Scientific Information Summary Epidemiology Environmental Characteristics Clinical Relevance Prevention and Therapy Molecular Aspects Diagnostic Relevance Compiled By

Component

d202 Der p 1

d202 Der p 1 Scientific Information

Type:

Component

Name; WHO/IUIS:

Der p 1

Biological function:

Group 1 (Cysteine protease)

Allergen code:

d202

Molecular Weight:

25 kDa

Route of Exposure:

Airway (Inhalation)

Source Material:

Located in the mid-gut and faecal particles of house dust mite. Native sourced from the extracts of Dermatophagoides pteronyssinus or recombinant

Other Names :

Antigen P1, DP1, Gorup 1 Mites

Summary

Der p 1 is one of the major allergens of house dust mite (HDM), with a reported prevalence among Dermatophagoides pteronyssinus (Der p) sensitized patients to be between 70-100%. The exposure of Der p 1 is through inhalation of the mite excrement. Early exposure of dust mite antigen Der p 1 increases the asthma risk up to fivefold. Decrease of the Der p 1 allergen exposure in mite allergic patients have reported a reduction in symptoms of rhinitis and asthma. A high degree of cross-reactivity with Der f 1 (from Dermatophagoides farinae, Der f) is reported. Der p 1 sensitization evaluation is considered important for the selection of patients suitable for specific immunotherapy (SIT).

Epidemiology

Worldwide distribution

Der p 1 is one of the major mite allergens of house dust mite (HDM) (1). The prevalence of Der p 1 among Dermatophagoides pteronyssinus sensitized patients is reported to be between 70-100%. Der p 1 is found to be present in the mite fecal particles and is strongly associated with asthma (2, 3).

Environmental Characteristics

Source and tissue

Der p 1 is the major allergen component extracted from the mite allergen crude extracts. It is found to be located in the mid-gut and fecal pellets of the Dermatophagoides pteronyssinus (4).

One of the novel methods used for purification or isolation of Der p 1 is Chromatography including chromatography on Resource Q column. The Fractions obtained from Resource Q column are usually confirmed and characterized by mass spectrometry. The molecule can also be generated by recombinant expression systems (5).

Risk factors

An elevation up to fivefold in the asthma risk is observed due to early exposure of the dust mite antigen Der p1 to individuals (6). According to a study conducted, the biological response to HDM allergen, Der p 1, is driven by targeting the sinonasal epithelium. Exposure of Der p 1 HDM antigen to sinonasal epithelium reduces the expression of tight junction proteins (TJPs). This expression in turn may escalate the permeability of antigens across the sinonasal epithelial layer, thus representing a potential mechanism for the exposure of the antigen in allergic rhinitis (7).

Clinical Relevance

Specific molecules

Der p 1 is a papain-like cysteine protease and is reported to be synthetized as a proenzyme. The proteolytic activity of Der p 1 is blocked due to the presence of a cysteine protease domain (222 residues) and an N-terminal pro-peptide (80 amino acids). The performance of pro-peptide of Der p 1, as an intramolecular chaperone, helps in its right folding and the extracellular secretion (8). Der p 1 in particular accounts for 22% of the total protease transcripts (9).

Cross-reactive molecules

A high degree of cross-reactivity pertaining to T-cell was observed between the group 1 and group 7 allergens of HDM denoted by the proliferative and cytokine response to the group 1 and group 7 allergens (10). Currently, in the literature, the structures of the Der p 1-specific epitopes for monoclonal antibodies (mAb) 5H8 and 10B9 are reported. The cross-reactivity between mAb 4C1 and Der p 1 was inhibited by the Der p 1-specific mAb 10B9, but not to Der f 1. In the study, most mAb produced against Der p 1 were directed to the identical epitope (mAb 5H8; 71.4%) and 4 were directed to a different epitope (mAb 10B9; 11.4%) (11).

Prevention and Therapy

Experimental trials

According to a meta-analysis of the five trials, major allergens including Der p 1 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, the effectiveness of the tablet was shown for a wide range of patients, and was explained by the presence of 1:1 ratio of the two major HDM allergens to which individuals were most frequently sensitized (12).

Molecular Aspects

Biochemistry

Der p 1 of HDM has a molecular weight of 25 kDa glycoprotein (13). The HDM allergens are reported to pass across the epithelial surface by disrupting the tight junction between the epithelial cells through the proteases present in the mites. The extracts of Der p 1 also demonstrate the desquamation of the epithelial cells in a protease-dependent manner which facilitates the entry of the allergen inside the airway wall. This process induces the release of pro-inflammatory cytokines (interleukin 6 and interleukin 8, through protease-activated receptors) in response to proteases present in HDM extract, leading to inflammatory responses (14).

Cross-reactivity

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. One of the main causes of cross-reactivity among mites, cockroaches, shellfish, helminths is due to Tropomyosin (Der p 10), however, glutathione transferase may also be included. In cases where genuine sensitization is unclear, specific allergen components can be useful to identify primary allergy (2).

The structural similarities between Der p 1 and Der f 1 were demonstrated with an X-ray crystal structure analysis. The analysis showed surface conservation of a crystal structure of natural Der f 1 with Der p 1 of 71% amino acid similarity along with an overlapping catalytic site. The structural similarities between Der p 1 and Der f 1 are commonly believed to be the basis for cross-reactivity among the 2 allergens (11, 15).

Diagnostic Relevance

Disease Severity

The measurement of IgE levels to native Der p 1 is a useful diagnostic tool for the assessment of genuine HDM allergy. A study was conducted in 55 DP-sensitized asthmatic patients, wherein, 89% positivity for IgE antibodies to native Der p 1was noted. The area under the receiver operating characteristic curves for IgE was found as a predictor of immediate asthmatic response (IAR) with a value of 0.913. The specificity of IgE to Der p 1 was higher than IgE to crude DP. IgE to Der p 1 was highly predictive of allergen-induced IAR (16).

AIT Prescription

Der p 1 sensitization evaluation is considered important for the selection of patients suitable for allergen immunotherapy using HDM extract (16).

Allergen components, including Der p 1 may be helpful in establishing the indication for AIT (17). According to a trial conducted, SLIT demonstrated its safety and effectiveness in primary house dust mite allergy-induced asthma in adolescents aged 14 years and in adults (18).

Exposure

The exposure is through inhalation of the mite fecal pellets. Exposure of Der p 1 is reported to exhibit cysteine protease activity that may result in epithelial cell desquamation, the release of cytokines, and in turn, leads to allergen expression across the epithelial cell layer. The desquamation further results in allergenic compound penetration deep into the airway wall (14).

Patients with mite allergy have reported a decrease in symptoms of rhinitis and asthma after an exposure reduction of the Der p 1 allergens from 13 μg/g to 0.2 μg/g (2).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Christian Fischer

Last reviewed: October 2020

References

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