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Whole Allergen

m207 Aspergillus niger

m207 Aspergillus niger Scientific Information

Type:

Whole Allergen

Display Name:

Aspergillus niger

Route of Exposure:

Respiratory

Family:

Trichocomaceae

Species:

niger

Latin Name:

Aspergillus niger

Other Names:

Aspergillus niger

Summary

Aspergillus niger is a filamentous fungus and is ubiquitous in the environment, in both the soil and as airborne spores. It is an economically important pathogen of crops and causes allergic and infectious diseases in humans. A niger allergens are important in occupational allergic disease and the pathophysiology of respiratory allergic disease, where there is a significant health burden. Exposure to the allergen is by the inhalational route. Although several A. niger specific allergenic proteins have been proposed, they are presently poorly understood. Cross-reactivity with other species of the Aspergillus genus is thought to be commonplace. 

Allergen

Nature

Aspergillus niger is a filamentous ascomycete fungus that belongs to the Aspergillus genus, species of which are an important cause of disease in humans and animals (1). Aspergillus spp. are also an important plant pathogen, with spoilage due to Aspergillus spp. resulting in significant economic losses (2). The pathogenicity or Aspergillus spp. is linked to inherent thermotolerance, which confers an ability to germinate in lung tissue (3). Aspergillus fumigatus is the most prevalent pathogenic species of the genus (4). However, A. niger is more commonplace in the environment than A. fumigatus (5). A. niger is morphologically distinguished from other species in the genus with black conidial heads and relatively large conidia (3–5 µm) (4).

In common with other species in the genus, A. niger has a worldwide distribution (6). However, there is a geographical variance in the prevalence of Aspergillus spp. (6). A study from India showed that A. niger was the most prevalent airborne Aspergillus fungus (26.4%). In contrast, in Madrid it was 11%(6). This geographical variation is thought to be due to climate, local ecology, and degree of urbanization and pollution (6). Finally, the same study found a seasonal pattern of A. niger colony counts (6).

A. niger products are used in various industries, from biofuel to baking and animal feed additives and seed treating plants (7). 

Taxonomy

Taxonomic tree of Aspergillus niger (5)

Domain

Eukaryote

Kingdom

Fungi

Phylum

Ascomycota

Subphylum

Pezizomycotina

Class

Eurotiomycetes

Family

Trichocomaceae

Genus

Aspergillus

Taxonomic tree of Aspergillus niger (5)

Epidemiology

Worldwide distribution 

The incidence of Aspergillus sensitization in patients with allergic respiratory disease has been reported between 15.3%– 38.0 % (8) and a risk factor for a more severe clinical disease course (9). It is estimated that up to 70% of patients with severe asthma are sensitized to fungi, compared with 10% of patients with milder disease and 5% of the general population (10). For patients with cystic fibrosis (CF), a meta-analysis reported a pooled prevalence of sensitization to Aspergillus spp of 39.1%. It should be noted that observed prevalence was higher with skin prick test than specific IgE assay (11). ABPA occurs in approximately 7-9% of CF patients and 1-2% asthmatic patients (12).

A study from India (8) found a high proportion of patients with asthma were sensitized to A. niger, with 68.7% having A. niger specific circulating IgE and 14.7% returning positive skin prick test (8). Another study from the UK reported A. niger had a prevalence of 8% of the total positive fungal culture from patients with non-cystic bronchiectasis (3).

With its widespread use in industry, A. niger allergens are also a well-described pathogenic cause of occupational asthma (OA) and hypersensitivity pneumonitis (13), with baker’s and animal feed producers most at affected (14). One study showed that 87.5% (n=7/8) bakers had IgE raised against an A. niger allergen, xylosidase (7).

Environmental Characteristics

Living environment

A. niger, is a soil-living organism (2) and is a causative factor in hypersensitivity pneumonitis due to occupational exposure of greenhouse workers and horticulturalists. A niger has been isolated from diverse horticultural substrates, including Rockwool, peat and coco fibre, as well as being airborne (13). The evidence for A. niger causing allergic respiratory disease is documented in a small series of case studies (13).

Route of Exposure

Main 

The primary route of exposure to A. niger is allergen inhalation (15). Aspergillus spp. have small conidiospores (2–5 µm), which means they can reach the terminal airways. However, their presence in the upper respiratory tract can also provoke a hypersensitivity reaction (6). 

Clinical Relevance

The spectrum of allergic diseases caused by Aspergillosis species includes asthma (with or without rhinitis), allergic rhinosinusitis and hypersensitivity pneumonitis (5). The significance of hypersensitivity to Aspergillus spp. in the pathogenesis of asthma is well described. Patients with asthma sensitized to Aspergillus spp. are more likely to have more severe clinical signs (9). Although type III and IV hypersensitivity is implicated in mold allergy, the main burden of the disease is the consequence of type I hypersensitivity (3).

 Severe disease is associated with increased morbidity and early mortality (3). The eosinophilic endotype associated with Aspergillus hypersensitivity is primarily seen in adults as late-onset asthma but can also be secondary to existing airway disease, such as cystic fibrosis (3).

Allergic bronchopulmonary aspergillosis (ABPA) is diagnosed when a specific set of clinical parameters are fulfilled (9), fixed airways obstruction, bronchiectasis, and lung fibrosis (3). ABPA can cause irreversible lung damage, and so there is an imperative to obtain a diagnosis as soon as practicable (15). Patients with ABPA are commonly sensitized to the Aspergillus fumigatus allergens, Asp f 1 and 2, which are helpful for diagnosis (15).

Molecular Aspects

Table adapted from Allergen.org (16)

Allergen name

Protein group (if known)

Size (kDa)

Asp n 3

Perioxisomal Protein

-

Asp n 4

-

-

Asp n 14

Beta - xylosidase

105

Asp n 18

Vacualoar serine protease

34

Asp n 25

3-phytase B

66-100 (84 Green & Beezhold, 2012)

Asp n 26

Acidic Ribosomal Protein 1

-

Asp n 30

Catalase

-

Asp n glucoasminase

Glucosaminase

68 (Green & Beezhold, 2012)

Asp n Hemicellulase

Xylanase

22.6 (Green & Beezhold, 2021)

Asp n Pectinase

Pectinase

-

Allergen name

Protein group (if known)

Size (kDa)

Allergenic molecules

The molecular basis of many A. niger allergens is well described in their context of occupational allergens. Glucoamylase, a dough additive used in industrial baking and production of high glucose syrups, has been reported to cause sensitization and OA. Furthermore, phytase, which is used in the manufacture of animal feed, is the allergen Asp n 25, as designated by the IUIS Allergen nomenclature committee. Phytase is highly sensitizing, and direct handling should be avoided (7).

The molecular characterization of Aspergillus allergens involved in the pathogenesis of ABPA is less well defined, in part because of lack of reagents, with only the A. fumigatus allergens Asp f 1-4 and Asp f 6 commercially available for diagnostic testing. There remains at present little information about the role of A. niger allergens in the pathogenicity of ABPA (3). However, a serine protease (Asp n 18) has been proposed as a potential major allergen (1). 

Cross-reactivity

There is evidence of significant cross-reactivity between allergens of different Aspergillus spp. (15) and it has been proposed that for many patients with ABPA who are positive for A fumigatus specific IgE, their clinical signs may be caused by another member of the Aspergillus genus  Although co-sensitization to both Aspergillus species may have occurred simultaneously (17).

A study has shown that all patients positive to IgEs specific to A. niger, A. flavus or A. terreus also had A. fumigatus specific IgE. However, it is thought that A. niger is less cross-antigenic with A. fumigatus than A. flavus (15). It has also been shown that A. niger has no cross-reactivity with Alternaria alternata, a clinically significant cause of fungal hypersensitivity (18). 

Compiled By

Author: RubyDuke Communications

Reviewer: Dr. Christian  Fischer

 

Last reviewed: December  2022

References
  1. Simon-Nobbe B, Denk U, Pöll V, Rid R, Breitenbach M. The Spectrum of Fungal Allergy. International Archives of Allergy and Immunology. 2008;145(1):58-86.
  2. Martínez J, Nevado A, Suñén E, Gabriel M, Vélez-Del-Burgo A, Sánchez P, et al. The Aspergillus niger Major Allergen (Asp n 3) DNA-Specific Sequence Is a Reliable Marker to Identify Early Fungal Contamination and Postharvest Damage in Mangifera indica Fruit. Front Microbiol. 2021;12:663323.
  3. Wardlaw AJ, Rick EM, Pur Ozyigit L, Scadding A, Gaillard EA, Pashley CH. New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease. J Asthma Allergy. 2021;14:557-73.
  4. Sugui JA, Kwon-Chung KJ, Juvvadi PR, Latgé J-P, Steinbach WJ. Aspergillus fumigatus and related species. Cold Spring Harb Perspect Med. 2014;5(2):a019786-a.
  5. Fukutomi Y, Taniguchi M. Sensitization to fungal allergens: Resolved and unresolved issues. Allergol Int. 2015;64(4):321-31.
  6. Vermani M, Vijayan V, Kausar A, Agarwal M. Quantification of Airborne Aspergillus Allergens: Redefining The Approach. The Journal of asthma : official journal of the Association for the Care of Asthma. 2010;47:754-61.
  7. Green BJ, Beezhold DH. Industrial fungal enzymes: an occupational allergen perspective. J Allergy (Cairo). 2011;2011:682574.
  8. Vermani M, Vijayan VK, Agarwal MK. Identification of Aspergillus (A. flavus and A. niger) Allergens and Heterogeneity of Allergic Patients' IgE Response. Iran J Allergy Asthma Immunol. 2015;14(4):361-9.
  9. Maurya V, Gugnani HC, Sarma PU, Madan T, Shah A. Sensitization to Aspergillus antigens and occurrence of allergic bronchopulmonary aspergillosis in patients with asthma. Chest. 2005;127(4):1252-9.
  10. Rick E-M, Woolnough KF, Seear PJ, Fairs A, Satchwell J, Richardson M, et al. The airway fungal microbiome in asthma. Clinical & Experimental Allergy. 2020;50(12):1325-41.
  11. Maturu VN, Agarwal R. Prevalence of Aspergillus sensitization and allergic bronchopulmonary aspergillosis in cystic fibrosis: systematic review and meta-analysis. Clin Exp Allergy. 2015;45(12):1765-78.
  12. Janahi IA, Rehman A, Al-Naimi AR. Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Ann Thorac Med. 2017;12(2):74-82.
  13. Madsen AM, Crook B. Occupational exposure to fungi on recyclable paper pots and growing media and associated health effects – A review of the literature. Science of The Total Environment. 2021;788:147832.
  14. Raulf M, Quirce S, Vandenplas O. Addressing Molecular Diagnosis of Occupational Allergies. Curr Allergy Asthma Rep. 2018;18(1):6.
  15. Kuwabara K, Hirose M, Kato K, Yokoi T, Shiga M, Kondo R, et al. Serological analysis of sensitization in allergic bronchopulmonary aspergillosis: a study on allergen components and interspecies relationships. J Asthma. 2020;57(6):610-7.
  16. Allergen.org. Asp 2021 [cited 2021 16.12.21]. Available from: http://www.allergen.org/search.php?allergenname=Asp&allergensource=&TaxSource=&TaxOrder=&foodallerg=all&bioname=.
  17. Harada K, Oguma T, Saito A, Fukutomi Y, Tanaka J, Tomomatsu K, et al. Concordance between Aspergillus-specific precipitating antibody and IgG in allergic bronchopulmonary aspergillosis. Allergol Int. 2018;67s:S12-s7.
  18. Twaroch TE, Curin M, Sterflinger K, Focke-Tejkl M, Swoboda I, Valenta R. Specific Antibodies for the Detection of Alternaria Allergens and the Identification of Cross-Reactive Antigens in Other Fungi. Int Arch Allergy Immunol. 2016;170(4):269-78.