Lep d 2
Summary
Lep d 2 is a major group 2 allergen found in the intestine and fecal pellets of a storage mite (SM), Lepidoglyphus destructor. It is responsible for occupational allergies among grain-storage workers, farmers, agricultural workers, and bakers in rural settings as well as humid urban dwellings. The allergic reactions manifested are moderate-to-severe asthma, allergic rhinitis, conjunctivitis, and atopic dermatitis. High IgE-mediated cross-reactivity was found among the different storage mite species while a limited cross-reactivity was found between storage mite and house dust mite allergens. The allergen exhibits cross-reactivity with Gly d 2 and Tyr p 2 from the species Glycyphagus domesticus and Tyrophagus putrescentiae, respectively, reflecting a closeness in their amino acid sequences.
Epidemiology
Worldwide distribution
Lep d 2 from Lepidoglyphus destructor is one of the most significant group 2 allergens of storage mites (SM),. Lep d 2 is associated with sensitization in allergic individuals due to occupational exposure or in rural and humid urban dwellings (20-30°C, >65% relative humidity).
Specific IgE against Lep d 2 is consistently identified in a high percentage of individuals who exhibit sensitization. In a recent study conducted in Spain with 150 adult patients (mean age 31.8 years) categorized according to their underlying atopic phenotype (such as allergic rhinitis [AR], allergic asthma, and atopic dermatitis [AD]), both house dust mites (HDMs) and SMs were found to be the most common airborne source of sensitization. Among SM allergens, Lep d 2 was the most frequently reported with a sensitization frequency of 76% (114/150 patients).
Another Spanish study conducted on 133 patients (median age 26.0 years) diagnosed with moderate-to-severe non-occupational type 2 (T2) persistent asthma and who had a positive skin prick test (SPT) to any SM reported that Lep d 2 was the most found SM allergen showing positive specific IgE in 83.45% (111/133) of patients, followed by other group 2 allergens, Gly d 2 of Glycyphagus domesticus (69.17%) and Tyr p 2 of Tyrophagus putrescentiae (47.37%).
Clinical Relevance
Disease severity
L. destructor plays a pivotal role in exacerbating respiratory allergic reactions, leading to pronounced disease severity. Symptoms associated with L. destructor sensitization often manifest prominently and include moderate-to-severe asthma, AR, conjunctivitis, and AD.
In a cross-sectional, multicenter study of 101 patients complaining of respiratory allergy symptoms, Lep d 2 was identified to be significantly more frequently associated with asthma than AR (43.5% vs. 13.5%). Moreover, it is also linked to the severity of the symptoms in patients with moderate-to-severe AR as compared to mild AR (33.3% vs. 12.1%).
Cross-reactive molecules
SMs are cross-reactive with each other; however, there exists very low cross-reactivity between SM and HDM. Studies have highlighted inhibitory interactions between extracts of different mite species, such as D. pteronyssinus and L. destructor, emphasizing the complex interplay and cross-inhibition phenomena among closely related mite extracts.
The IgE inhibition experiments found a high level of IgE-mediated cross-reactivity among the different SM species. An extensive cross-reactivity was observed between the group 2 allergens Lep d 2 and Gly d 2, and Tyr p 2, but limited cross-reactivity was seen between Lep d 2 and Der p 2 (Dermatophagoides pteronyssinus), a major allergen of HDM.
Diagnostics
Disease Severity
Lep d 2 can be considered as a potential biomarker for detecting mild asthma cases as significant differences were seen mainly in moderate asthma compared to the severe cases. It was reported that IgE response to Der p 2 can be seen in more than 90% of patients with moderate-to-severe T2 persistent asthma (n=133), and more than half of these patients were co-sensitized to Lep d 2 and other group 2 allergens, such as Gly d 2 and Tyr p 2. Fewer patients (16.52%) were found to be sensitized to Lep d 2 and Der p 2 due to a low sequence homology.
Cross-Reactivity
The extracts of L. destructor and G. domesticus demonstrated a substantial level of cross-inhibition due to phylogenetic closeness of these mite species.
Exposure
The main route of allergen exposure is through the airway via inhalation of allergens present in fecal pellets of the mite species.
Explained Results
Allergen Information
Lep d 2, a 16-kDa protein, belongs to the group 2 allergen of L. destructor and is one of the most commonly found SM allergens.
Clinical relevance
Typical allergic reactions to Lep d 2 include bronchial asthma, allergic rhinitis, conjunctivitis, and AD due to inhalation of contaminated fecal pellets.
Cross-reactivity
A significant cross-reactivity between Lep d 2, Gly d 2, and Tyr p 2 has been reported due to close sequence similarity. L. destructor and G. domesticus exhibit a substantial level of cross-reactivity in their extracts.
Author: Turacoz Reviewed: Dr. Ulrica Olsson
References
- Cuevas, Mandy, Polk, Marie-Luise, Becker, Sven, Huppertz, Tilman, Hagemann, Jan, Bergmann, Christoph, Wrede, Holger, Schlenter, Wolfgang, Haxel, Boris, Bergmann, Karl-Christian and Klimek, Ludger (2022). "Rhinitis allergica in storage mite allergy." Allergo Journal International 31(3): 59-68.
- Eriksson, T. L., Gafvelin, G., Elfman, L. H., Johansson, C., Van Hage-Hamsten, M. and Olsson, S. (2001). "T cell responses to recombinant isoforms, synthetic peptides and a mutant variant of Lep d 2, a major allergen from the dust mite Lepidoglyphus destructor." Clin Exp Allergy 31(12): 1881-1890.
- Fernandez-Caldas, E., Puerta, L. and Caraballo, L. (2014). "Mites and allergy." Chem Immunol Allergy 100: 234-242.
- Gafvelin, G., Johansson, E., Lundin, A., Smith, A. M., Chapman, M. D., Benjamin, D. C., Derewenda, U. and van Hage-Hamsten, M. (2001). "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 107(3): 511-518.
- Gonzalez-Perez, R., Poza-Guedes, P., Pineda, F., Castillo, M. and Sanchez-Machin, I. (2022). "Storage Mite Precision Allergy Molecular Diagnosis in the Moderate-to-Severe T2-High Asthma Phenotype." Int J Mol Sci 23(8).
- Gonzalez-Perez, R., Poza-Guedes, P., Pineda, F., Galan, T., Mederos-Luis, E., Abel-Fernandez, E., Martinez, M. J. and Sanchez-Machin, I. (2023). "Molecular Mapping of Allergen Exposome among Different Atopic Phenotypes." Int J Mol Sci 24(13).
- Hilger, C., Kuehn, A., Raulf, M. and Jakob, T. (2014). "Cockroach, tick, storage mite and other arthropod allergies: Where do we stand with molecular allergy diagnostics?: Part 15 of the Series Molecular Allergology." Allergo J Int 23(6): 172-178.
- Kaiser, L., Gafvelin, G., Johansson, E., van Hage-Hamsten, M. and Rasool, O. (2003). "Lep d 2 polymorphisms in wild and cultured Lepidoglyphus destructor mites." Eur J Biochem 270(4): 646-653.
- Marques, M. L., Rezende, I., Cunha, I., Gouveia, J., Rodrigues Dos Santos, F., Falcao, I., Cunha, L. and Falcao, H. (2022). "Allergic sensitization to Storage Dust Mites: a prospective study of patients with respiratory allergy." Eur Ann Allergy Clin Immunol 54(1): 43-47.
- Sigsgaard, T., Basinas, I., Doekes, G., de Blay, F., Folletti, I., Heederik, D., Lipinska-Ojrzanowska, A., Nowak, D., Olivieri, M., Quirce, S., Raulf, M., Sastre, J., Schlunssen, V., Walusiak-Skorupa, J. and Siracusa, A. (2020). "Respiratory diseases and allergy in farmers working with livestock: a EAACI position paper." Clin Transl Allergy 10: 29.
- Solarz, K. and Pajak, C. (2019). "Risk of exposure of a selected rural population in South Poland to allergenic mites. Part II: acarofauna of farm buildings." Exp Appl Acarol 77(3): 387-399.
- Til-Perez, G., Carnevale, C., Sarria-Echegaray, P. L., Arancibia-Tagle, D., Chugo-Gordillo, S. and Tomas-Barberan, M. D. (2019). "Sensitization profile in patients with respiratory allergic diseases: differences between conventional and molecular diagnosis (a cross-sectional study)." Clin Mol Allergy 17: 8.
- WHO/IUIS. (2023, 2023-11-09 ). "ALLERGEN NOMENCLATURE." Retrieved December 29, 2023, from https://allergen.org/viewallergen.php?aid=404.
- Zhang, C., Li, J., Lai, X., Zheng, Y., Gjesing, B., Spangfort, M. D. and Zhong, N. (2012). "House dust mite and storage mite IgE reactivity in allergic patients from Guangzhou, China." Asian Pac J Allergy Immunol 30(4): 294-300.