Der p 2
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). 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.
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.
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.
Cross-reactive molecules
A high degree of cross-reactivity between Der p 2 and Der f 2 (from Dermatophagoides farinae) was found. 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.
Diagnostics
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.
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%.
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.
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.
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.
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.
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. 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.
References
- Reginald K. The major allergen Der p 2 is a cholesterol binding protein. Sci Rep 9, 1556 (2019) https://doiorg/101038/s41598-018-38313-9. 2019.
- Yeh C. High prevalence of IgE sensitization against house dust mites in pregnant women. Medicine (Baltimore). 2018;97(51):e13293.
- Platts-Mills TA, Vervloet D, Thomas WR, Aalberse RC, Chapman MD. Indoor allergens and asthma: report of the Third International Workshop. J Allergy Clin Immunol. 1997;100(6 Pt 1):S2-24.
- Park GM, Lee SM, Lee IY, Ree HI, Kim KS, Hong CS, et al. Localization of a major allergen, Der p 2, in the gut and faecal pellets of Dermatophagoides pteronyssinus. Clin Exp Allergy. 2000;30(9):1293-7.
- Platts-Mills TAE, Schuyler AJ, Erwin EA, Commins SP, Woodfolk JA. IgE in the diagnosis and treatment of allergic disease. J Allergy Clin Immunol. 2016;137(6):1662-70.
- Wang H. Evaluation of the Role of IgE Responses to Der p 1 and Der p 2 in Chinese House Dust Mite-Allergic Patients. Int Arch Allergy Immunol 2015;167:203-210. 2015.
- Tsai. 398 Detection of DER P 2 in the House Dust and Correlation with Mite Number in an Environmental Survey. . World Allergy Organ J 2012;5(Suppl 2):S144 Published 2012 Feb 17 doi:101097/01WOX0000412161626062b. 2012.
- Panzner P, Vachova M, Vlas T, Vitovcova P, Brodska P, Maly M. Cross-sectional study on sensitization to mite and cockroach allergen components in allergy patients in the Central European region. Clin Transl Allergy. 2018;8:19.
- Gafvelin G, Johansson E, Lundin A, Smith AM, Chapman MD, Benjamin DC, et al. Cross-reactivity studies of a new group 2 allergen from the dust mite Glycyphagus domesticus, Gly d 2, and group 2 allergens from Dermatophagoides pteronyssinus, Lepidoglyphus destructor, and Tyrophagus putrescentiae with recombinant allergens. J Allergy Clin Immunol. 2001;107(3):511-8.
- Nolte, Plunkett G, Grosch K, Larsen JN, Lund K, Bollen M. Major allergen content consistency of SQ house dust mite sublingual immunotherapy tablets and relevance across geographic regions. Ann Allergy Asthma Immunol. 2016;117(3):298-303.
- González-Pérez. Evaluation of major mite allergens from European standardized commercial extracts for in vivo diagnosis: addressing the need for precision medicine. Clin Transl Allergy 9, 14 (2019). 2019.
- Lin. Aeroallergen Der p 2 induces apoptosis of bronchial epithelial BEAS-2B cells via activation of both intrinsic and extrinsic pathway. Cell Biosci 5, 71 (2015) https://doiorg/101186/s13578-015-0063-5. 2015.
- WHO/IUIS. Der p 2 allergen nomenclature 2019 [10-08-2020]. Available from: http://www.allergen.org/viewallergen.php?aid=289.
- Reginald K, Chew FT. Conformational IgE Epitope Mapping of Der p 2 and the Evaluations of Two Candidate Hypoallergens for Immunotherapy. Sci Rep. 2018;8(1):3391.
- Bordas-Le Floch V, Bussieres L, Airouche S, Lautrette A, Bouley J, Berjont N, et al. Expression and characterization of natural-like recombinant Der p 2 for sublingual immunotherapy. Int Arch Allergy Immunol. 2012;158(2):157-67.
- Park JW. Cross-reactivity of Tyrophagus putrescentiae with Dermatophagoides farinae and Dermatophagoides pteronyssinus in urban areas. Annals of Allergy, Asthma & Immunology. 1999;Volume 83, Issue 6, December 1999, Pages 533-539.
- ReginaldK. Blo t 2: Group 2 allergen from the dust mite Blomia tropicalis. Sci Rep 9, 12239 (2019) 2019.
- Minami T, Fukutomi Y, Lidholm J, Yasueda H, Saito A, Sekiya K, et al. IgE Abs to Der p 1 and Der p 2 as diagnostic markers of house dust mite allergy as defined by a bronchoprovocation test. Allergol Int. 2015;64(1):90-5.
- Peixoto S. Evaluation of sensitization to Derp1 and Derp2 in a pediatric population of the North of Portugal. An Pediatr (Barc) 2018 Sep;89(3):162-169 doi: 101016/janpedi201710014. 2018.
- Osterlund C, Gronlund H, Polovic N, Sundstrom S, Gafvelin G, Bucht A. The non-proteolytic house dust mite allergen Der p 2 induce NF-kappaB and MAPK dependent activation of bronchial epithelial cells. Clin Exp Allergy. 2009;39(8):1199-208.