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Component

d207 Blo t 5

d207 Blo t 5 Scientific Information

Type:

Component

Name; WHO/IUIS:

Blo t 5

Biological function:

Unknown

Allergen code:

d207

Molecular Weight:

14 kDa

Other Names :

Blomia tropicalis 5

Whole Allergen: Blomia tropicalis

Summary

Blomia tropicalis 5 (Blo t 5), a major allergen found in the gut and fecal pellets of a common dust mite, B. tropicalis, causes allergic reactions in 70-92% of patients with mite allergy in tropical climates. The probable risk factors for Blo t 5 sensitizations include environmental and climatic factors, genetic predisposition, and exposure to indoor dust. The literature has demonstrated the association of Blo t 5 with several symptoms ranging from mild to severe reactions such as asthma, allergic rhinitis, conjunctivitis, atopic dermatitis, and even oral mite anaphylaxis. Studies have reported its correlation with disease severity in patients with asthma and atopic dermatitis. Blo t 5 is a 14 kDa monomeric allergen with a predominant α-helical structure Despite structural similarities with Blo t 21 and Der p 5, Blo t 5 shows limited to moderate cross-reactivity with Blo t 21 and Der p 5.

Epidemiology

Worldwide distribution

Blomia tropicalis 5 (Blo t 5) is one of the major allergens of Blomia tropicalis (B. tropicalis), a common dust mite, that mostly inhabits tropical, subtropical, and temperate regions characterized by elevated humidity and warm temperatures (Hussein et al. 2015, Jeevarathnum et al. 2015, Santos da Silva 2017). In tropical climates, Blo t 5 has been found to induce allergic reactions in around 70-92% of individuals with mite allergies, establishing it as the primary group-5 allergen linked to reactions in this climate (Kim et al. 2015).

A prospective study from Singapore including 253 children (mean age: 7.3 years) with symptoms of allergic rhinitis (AR), asthma, and atopic dermatitis (AD) reported that 70% of these children were sensitized to B. tropicalis and among them, 45% showed positive IgE responses to Blo t 5 (Kidon et al. 2011).

Environmental characteristics       

Source and tissue

Blo t 5 is a lipid-binding protein secreted by the stomach walls and gut epithelium of B. tropicalis. Studies have shown its presence in the epithelial lining of the hindgut lumen, digestive substances of the midgut, and fecal pellets (Bi et al. 2005, Gao et al. 2007, Sanchez-Borges et al. 2017).

Risk factors

Genetic predisposition, immune sensitization, climatic conditions in tropical and subtropical regions (like high humidity and warm temperatures), and exposure to indoor dust are considered to be the probable risk factors for developing sensitization to Blo t 5 (Jeevarathnum et al. 2015, Sanchez-Borges et al. 2017, Santos da Silva 2017, Caraballo et al. 2020). Occupational exposure to B. tropicalis (such as in agricultural fields, retail stores, and bakeries) and house dust containing mite allergens may pose an increased risk of developing allergies (Hussein et al. 2015, Sanchez-Borges et al. 2017).

Clinical relevance

Disease severity

Blo t 5 has been linked to sensitization and allergic symptoms in patients with AR and asthma (Pauli et al. 2023). Cutaneous manifestations such as AD are also found to be associated with Blo t 5 (Camargo Lopes de Oliveira et al. 2019).

A sub-analysis of a nested case-control study was conducted in Columbia in 570 individuals (272 cases with current or past symptoms of asthma and 298 control) to report the prevalence of sensitization of different allergens from B. tropicalis. The findings suggested that sensitization to Blo t 5 was significantly greater in the asthmatic patients than the control group, thus confirming a strong association of Blo t 5 with asthma (Zakzuk et al. 2023).

Evidence suggest a correlation between Blo t 5 level and disease severity in asthma patients with greater IgE reactions to Blo t 5 observed in severe asthma as compared to milder disease (Pauli et al. 2023).

B. tropicalis allergens are also often associated with AR and conjunctivitis (Celakovska et al. 2021, Mourao et al. 2021).

B. tropicalis allergens are also commonly linked to AD (Camargo Lopes de Oliveira et al. 2019, Emran et al. 2019). A study from Brazil enrolled 59 patients with AD (median age: 8.4 years; mild AD, n=29; severe AD, n=30) to determine the patterns of sensitization in mild and severe forms of AD. The positivity rate for recombinant Blo t 5 (rBlo t 5) in immunoassay was significantly higher in patients with severe AD (83.3%) as compared to mild AD (41.4%). Furthermore, rBlo t 5 showed maximum correlation with the disease severity (Camargo Lopese Oliveira et al. 2019).   

The influence of B. tropicalis allergens is also found to be particularly prominent in children (Kidon et al. 2011). Another rare but severe symptom related to Blo t 5 allergen is oral mite anaphylaxis (OMA), also known as pancake anaphylaxis (Hussein et al. 2015, Sanchez-Borges et al. 2017). OMA is comparatively a newer syndrome that was found to occur immediately following the consumption of pancake made of flour contaminated with mites and is more common in tropical and subtropical areas where warm and humid climate is conducive for mites (Sanchez-Borges et al. 2017).

Cross-reactive molecules

A limited IgE cross-reactivity has been observed between Blo t 5 and Der p 5 from Dermatophagoides pteronyssinus (Kuo et al. 2003).

A study examined degree of cross-reactivity among recombinant group 5 and group 21 allergens of B. tropicalis (rBlo t 5 and rBlo t 21), Dermatophagoides farina (rDer f 5 and rDer f 21), and Tyrophagus putrescentiae (rTyr p 5 and rTyr p 21) and IgE inhibition to each allergen using a competitive ELISA technique. The IgE reactivity to rBlo t 5 was suppressed by approximately 86.99% due to rDer f 21, around 77.35% with rTyr p 5, and by 73.44% with rTyr p 21. The study results suggested cross-reaction is attributed to most of the IgE reactivity to group-5 and group-21 allergens of mite species (Kim et al. 2015).

Molecular aspects    

Biochemistry

Blo t 5, a 14kDa group 5 mite allergen, is the most thoroughly investigated and comprehensively characterized component from B. tropicalis (WHO/IUIS. 2003, Santos da Silva 2017, Caraballo et al. 2020). Blo t 5 exhibits unique sequence features including 15.4% positively charged residues, 22.2% negatively charged residues, and low extinction coefficients attributed to the absence of tryptophan residue (Santos da Silva 2017).

Structurally, Blo t 5 present a predominant a-helical structure, and the allergen has been determined to be monomeric (Santos da Silva 2017).

Blo t 5 consists of over 40% charged and 20% polar residues, the presence of these solvent-accessible residues facilitate better antibody binding, thereby affecting its allergenicity (Gao et al. 2007).

Isoforms, epitopes, antibodies

Currently one isoform of Blo t 5 has been identified, Blo t 5.0101 (WHO/IUIS. 2003).

A study has identified two epitopes recognized by Blo t 5 specific CD4 T cells (Wong et al. 2017). The amino-terminal end of Blo t 5 has been found to contain crucial IgE epitopes (Jiménez et al. 2007).

Another study concluded that recombinant Blo t 5 contains epitopes, recognized by IgE antibodies of B. tropicalis-sensitized patients (Carvalho Kdos et al. 2013).

Cross-reactivity due to structural similarity

Blo t 5 shares 39% identity with Blo t 21 with similarities in their primary and secondary structure with typical features of α-helical proteins (Gao et al. 2007). An average cross-reactivity between Blo t 5 and Blo t 21 lies between low to moderate; however, in some cases, it may be higher (Zakzuk et al. 2023). Both allergens harbor significant conserved IgE epitopes identified by IgE antibodies in B. tropicalis-sensitized patients (Carvalho Kdos et al. 2013, Kim et al. 2015).

The co-sensitization rate is reported to be high between Blo t 5 and Blo t 21. A Colombian study confirmed 80.3% Blo t 21 co-sensitization in Blo t 5-sensitized patients (Zakzuk et al. 2023).

Blo t 5 exhibits 43% amino acid sequence identity with Der p 5 but shows low-to-moderate cross-reactivity (Mourao et al. 2021).

A study by Kim and colleagues showed that Tyr p 5 and Blo t 5 displayed 52.9% sequence identity. The IgE reactivity of Blo t 5 was inhibited by up to 77.35% by rTyr p 5, suggesting high levels of cross-reactivity among the allergens (Kim et al. 2015).

Diagnostic relevance

Disease severity

An African study with 59 children and young adults (age 2-18) with confirmed asthma, found a high IgE-binding frequency for rBlo t 5 (37%). The study also confirmed that the majority of the patients with IgE reactivity to rBlo t 5 contained high levels of Blo t 5-specific IgE (Pauli et al. 2023).

A study from Brazil has reported that Blo t 5 may be associated with severe AD manifestation (Camargo Lopes de Oliveira et al. 2019).

Blo t 5 had higher rate of sensitization as compared to Der p 5 from D. pteronyssinus in a population from South China (D'Souza et al. 2021). Blo t 5 has been reported as a potential marker for accurate discrimination of IgE sensitization to Blomia and Dermatophagoides species (D'Souza et al. 2021).

Cross-reactivity

Analysis of cross-reactivities of rBlo t 5 and rBlo t 21 with the B. tropicalis extracts suggests that these allergens can be used as valuable markers for diagnosing B. tropicalis-sensitized patients (Santos da Silva 2017).

Exposure

The primary pathway for exposure to Blo t 5 is through airway inhalation (WHO/IUIS. 2003). However, Blo t 5 allergic manifestations can be triggered in numerous atopic individuals through the oral ingestion of contaminated food (Hussein et al. 2015). A study carried out in Egypt confirmed Blo t 5 to be present in several types of raw and processed food products such as wheat, corn, rice, cakes, rusks, pasta, etc. (Hussein et al. 2015).

Explained results:

Allergen Information

Blo t 5, a 14 kDa allergen, is found in the gut and fecal pellets of B. tropicalis and presents as one of the significant allergens from the species. It is responsible for allergic manifestations in patients with mite allergy in tropical, subtropical, and temperate regions with warm and humid climates (WHO/IUIS. 2003, Hussein et al. 2015, Santos da Silva 2017).

Clinical relevance

Patients with sensitization to Blo t 5 may experience problems including asthma, AR, and AD (Camargo Lopes de Oliveira et al. 2019, Pauli et al. 2023, Zakzuk et al. 2023).

Cross-reactivity

Cross-reactivity of IgE is seen among group-5 and group-21 allergens of different mite species (Kim et al. 2015, Camargo Lopes de Oliveira et al. 2019, Pauli et al. 2023, Zakzuk et al. 2023). However, Blo t 5 exhibits low-to-moderate cross-reactivity with Blo t 21 and Der p 5, despite sharing 39% and 41% sequence similarity with the allergens, respectively (Gao et al. 2007, Zakzuk et al. 2023).

 

Author: Turacoz

Reviewed: Dr. Ulrica Olsson

References
  1. i, X. Z., Gao, Y. F. and Chew, F. T. (2005). "Blo t 5, the major allergen from dust mite Blomia tropicalis, is secreted from the mite stomach and gut epithelial and is associated with gut and fecal contents." Journal of Allergy and Clinical Immunology 115(2).
  2. Camargo Lopes de Oliveira, L., Pierotti, F. F., Mallozi, M., Rodrigues Cocco, R., Rosario, N., Rugue Genov, I., Aberg, K. M., Borres, M. P. and Sole, D. (2019). "rBlo t 5 is a potential contributor to the severity of atopic dermatitis in a Brazilian population." Pediatr Allergy Immunol 30(5): 575-579.
  3. Caraballo, L., Valenta, R., Puerta, L., Pomes, A., Zakzuk, J., Fernandez-Caldas, E., Acevedo, N., Sanchez-Borges, M., Ansotegui, I., Zhang, L., van Hage, M., Abel-Fernandez, E., Karla Arruda, L., Vrtala, S., Curin, M., Gronlund, H., Karsonova, A., Kilimajer, J., Riabova, K., Trifonova, D. and Karaulov, A. (2020). "The allergenic activity and clinical impact of individual IgE-antibody binding molecules from indoor allergen sources." World Allergy Organ J 13(5): 100118.
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  5. Celakovska, J., Bukac, J., Cermakova, E., Vankova, R., Skalska, H., Krejsek, J. and Andrys, C. (2021). "Analysis of Results of Specific IgE in 100 Atopic Dermatitis Patients with the Use of Multiplex Examination ALEX2-Allergy Explorer." Int J Mol Sci 22(10).
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