Alternaria alternata

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Booklet: Native & Recombinant Allergen Components.
Allergy - Which allergens? Phadia AB, 2006.

 

Latin name
Alternaria alternata/Alternaria tenus

 

Summary

A. alternata, growing commonly on vegetation, is a member of the imperfect fungi and is one of the most important among the allergenic fungi. Brown segmented mycelia give rise to simple or solitary conidiophores, which may produce either solitary apical spores or a string of spores. The spores produced by imperfect fungi vary in shape, size, texture, colour, number of cells, and thickness of the cell wall (3). Although other Alternaria species are probably also relevant clinically, most research has been directed toward A. alternata.
 
Alternaria is one of the main allergens affecting children. In temperate climates, airborne Alternaria spores are detectable from May to November, with peaks in late summer and autumn (4). Dispersion of Alternaria spores occurs during dry periods. These feature higher wind velocity and lower relative humidity, which result in peak dispersion during sunny afternoon periods (5).
 
Despite the large spore size, spore dispersal may occur for hundreds of miles from the source. Counts of Alternaria on dry, windy days can be in the range of 500 to 1,000 spores per cubic metre in grass- or grain-growing areas. Outdoor spore counts of up to 7500 spores per cubic metre of air were associated with indoor spore counts between 0 and 280 per cubic metre (6). Significant concentrations of Alternaria allergens, between 3.0 and 1000 U/g of dust, have been found in house dust of allergic children, supporting the hypothesis that fungal allergen exposure is an important component in the pathogenesis of asthma (7-8). Alternaria can also be found in house dust samples in the absence of outdoor environmental mould spores (9).
 
Sensitivity to Alternaria, a potent allergen, has been increasingly recognised as a risk factor for the development, persistence, and exacerbation of asthma (10-15).
 
Studies have suggested that sensitivity to Alternaria may be a risk factor for life-threatening asthma (14, 16-17). In a study of 11 children and young adults aged 11 to 25 years with asthma who had sudden respiratory arrest, exposure to this aeroallergen was reported to be a significant risk factor (5). The influence of ambient Alternaria spores on emergency department visits for children with acute asthma exacerbations has also been demonstrated (18-19).
 
Furthermore, asthma in children with Alternaria sensitivity was reported to persist beyond the age of 11, compared to asthma in individuals who were negative (20). In the USA, up to 80% of subjects with confirmed asthma have demonstrated positive reactions to 1 or more fungi (21-22), and up to 70% of patients with fungal allergy have skin sensitisation to Alternaria (10). The highest concentrations of spores are in grain-growing areas such as the Midwest (5). Nevertheless, in a study of 12,086 asthmatic children residing in US inner cities, 38.3% had positive skin test reactions to Alternaria species (23).
 
Studies in Europe have also evaluated Alternaria sensitisation. In an epidemiological survey in 30 centres across Europe, the frequency of sensitisation to moulds (Alternaria alternata, Cladosporium herbarum, or both) increased significantly with increasing asthma severity in all of the regions studied, although there were differences in the frequency of sensitisation. Researchers concluded that sensitisation to moulds is a powerful risk factor for severe asthma in adults (24).
 
Alternaria-sensitised patients may also be at risk for allergic rhinitis (25). Many severe cases of rhinitis may be attributable to Alternaria sensitivity (26). Fungal components may upon skin contact cause eczema or trigger inflammatory skin eruptions in a subgroup of patients with atopic eczema (27), although other Alternaria allergens may be important in atopic dermatitis (28). Infrequently, hypersensitivity pneumonitis has also been attributed to this organism (29).
 
The significance of Alternaria as an important aeroallergen in respiratory allergy has been documented in a number of other European studies (30-38), and also throughout the world (13-14, 39-43).
 
Alternaria sensitisation may occur in occupational settings, including gardens, bakeries, forests and farms. Occupational asthma may be precipitated by fungal spores of Alternaria, Macrosporium and Stemphylium during Asparagus and Strawberry harvesting times throughout the year. Alternaria is associated with baker's asthma and wood pulp worker's lung. In a study evaluating 3 types of farming activities, including animal feeding on a hog farm, cleaning and animal handling on a dairy farm, and Soybean unloading and handling on a grain farm, grain unloading and handling activity generated the highest concentrations of airborne fungi, compared to the other 2 activities (44). Air contamination inside greenhouses is mainly related to moulds, and is facilitated by the high indoor temperature and humidity. Cladosporium, Penicillium, Aspergillus, Alternaria and a wide range of flower pollens can sensitise greenhouse workers and cause occupational asthma (45).
 
Mould allergy diagnoses are performed with fungal extracts consisting of a complex mixture of proteins, glycoproteins, polysaccharides, and other substances; these extracts often show a considerable variability as a result of inter-strain genomic differences, different culture conditions, and variable extraction procedures (46-47). It is very difficult to grow 2 consecutive cultures with similar antigenic profiles (48). Thus, the number of allergens in A. alternata extracts may range from 10 to 30, and few allergens are present in nearly all extracts studied (49). The presence of specific allergens, including the major allergens, depends very much on the growth conditions, and may vary during the growth cycle, being greater one day than another (50-51).
 
 
Furthermore, the major allergens are secreted proteins, whereas the other allergens are intracellular proteins, and the latter are presented to the immune system in the spores of this mould, which are too large to reach the alveoli of the lung (50). Furthermore, germination of spores significantly increases allergen release (but not all spores release allergens). For example, Alt a 1, the major allergen, may be a minor contributor to the total amount of allergens released from spores, except when spores have germinated (52).
 
How the phenomena revealed in these results reflect the allergen content of spores in the air that we breathe has, however, not been fully elucidated. Nevertheless, advances in molecular biology have led to a better understanding of these allergens and their relationship to allergic disease (53).
 
Although it is clear from a number of epidemiologic studies that sensitisation to indoor allergens and to the spores of Alternaria are risk factors for the development of asthma in both children and adults (54), detailed investigation is problematic. Many studies have utilised serum-specific IgE and skin-specific IgE determination, but, as already discussed, there are inherent difficulties in the manufacturing and standardising of fungal extracts (55), and variability in epidemiologic studies inevitably results (10). Non-standardised mould extracts may also result in poor outcomes in specific immunotherapy (56).
 
Therefore, diagnostic and therapeutic procedures with purified allergens may be of benefit. Recombinant mould allergens of suitable purity and consistency can be produced. Some have become standardised diagnostic material and may be of benefit in component-resolved diagnosis.
 
Allergens:
  • Alt a 1, a 29.2-31 kDa major allergen, a heat-stable protein (1, 50, 57-73)
     
  • Alt a 2, a 25 kDa protein, a major allergen, an aldehyde dehydrogenase (1-2, 69-73)
     
  • Alt a 3, a heat shock protein (1, 50, 69-70, 72)
     
  • Alt a 4 (1, 50, 69-71)
     
  • Alt a 5, a 47 kDa protein, an enolase (formerly Alt a 11) (1, 69-70, 74-79)
     
  • Alt a 6, a 11 kDa protein, an acid ribosomal protein P2 (1, 49, 69-70, 72, 80)
     
  • Alt a 7, a 22 kDa protein, a YCP4 Protein (1, 69-70, 72)
     
  • Alt a 8 (69, 71)
     
  • Alt a 9 (69, 71)
     
  • Alt a 10, a 53 kDa protein, an aldehyde dehydrogenase (1, 21, 69-70, 72)
     
  • Alt a 11, now reclassified as Alt a 5
     
  • Alt a 12, a 12, an acid ribosomal protein P1 (1, 70)
     
  • Alt a 13, a glutathione-S-transferase (81)
     
  • Alt a 70kD, a 70 kDa protein (82-83)
     
  • Alt a NTF2, a nuclear transport factor 2 protein (84)

References:

     
2006