Der p 1
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). 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.
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. Der p 1 in particular accounts for 22% of the total protease transcripts.
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. 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%).
Diagnostics
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.
AIT Prescription
Der p 1 sensitization evaluation is considered important for the selection of patients suitable for allergen immunotherapy using HDM extract.
Allergen components, including Der p 1 may be helpful in establishing the indication for AIT. 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.
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.
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.
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.
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.
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.
References
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