rAlt a 1

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Alternaria alternata m6

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Code: m229
Latin name: Alternaria alternata/Alternaria tenuis
Source material: rAlt a 1 is a CCD-free recombinant protein
Common names: Alt-1

Alternaria alternata allergen components

Available ImmunoCAP®:

Summary

A. alternata (syn. A. tenius), 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 (1). Although other Alternaria species are probably also relevant clinically, most research has been directed toward A. alternata, in particular as a result of cross-reactivity of the species.

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 (2). 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 (3).

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 7,500 spores per cubic metre of air were associated with indoor spore counts between 0 and 280 per cubic metre (4). Significant concentrations of Alternaria allergens, between 3.0 and 1,000 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 (5-6). Recently, Alternaria has been found in house dust samples in the absence of outdoor environmental mould spores (7).
Sensitivity to Alternaria, a potent allergen, has been increasingly recognised as a risk factor for the development, persistence, and exacerbation of asthma (8-13).

Mould allergy diagnoses are performed with fungal extracts consisting of a complex mixture of proteins, glycoproteins, polysaccharides, and other substances; these extracts show a considerable variability as a result of inter-strain genomic differences, different culture conditions, and variable extraction procedures (14-15). It is almost impossible to grow 2 consecutive cultures with similar antigenic profiles (16). 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 (17). 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 (18-19).

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 (18). 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 (20). 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 (21).

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 (22), detailed investigation is problematic. Many studies have utilised skin test and IgE antibody determination, but, as already discussed, there are inherent difficulties in the manufacturing and standardising of fungal extracts (23), and variability in epidemiologic studies inevitably results (8). Non-standardised mould extracts may also result in poor outcomes in specific immunotherapy (24).

Therefore, diagnostic and therapeutic procedures with purified allergens may be of benefit. Recombinant mould allergens of suitable purity and consistency can be produced. They have become standardised diagnostic material and may be of benefit in component-resolved diagnosis.

The following allergens have been characterised:

  • Alt a 1, a 29.2-31 kDa major allergen, a heat-stable protein (18,25-42).
     
  • Alt a 2, a 25 kDa protein, a major allergen, an aldehyde dehydrogenase (25,38-43).
     
  • Alt a 3, a heat shock protein (18,25,38-39,41).
     
  • Alt a 4 (18,25,38-40).
     
  • Alt a 5, a 47 kDa protein, an enolase (formerly Alt a 11) (25,38,39,43,48).
     
  • Alt a 6, a 11 kDa protein, an acid ribosomal protein P2 (17,25,38-39,41,49).
     
  • Alt a 7, a 22 kDa protein, a YCP4 Protein (25,38-39,41).
     
  • Alt a 8 (38-40).
     
  • Alt a 9 (38-40).
     
  • Alt a 10, a 53 kDa protein, an aldehyde dehydrogenase (25,38-39,41,50).
     
  • Alt a 11, now reclassified as Alt a 5.
     
  • Alt a 12, a 12, an acid ribosomal protein P1 (25,39).
     
  • Alt a 13, a glutathione-S-transferase (51).
     
  • Alt a 70kD, a 70 kDa protein (52-53).
     
  • Alt a NTF2, a nuclear transport factor 2 protein (54).
     
Allergens from Alternaria alternata listed by IUIS*
Alt a 1 Alt a 3 Alt a 4
Alt a 5 Alt a 6 Alt a 7
Alt a 8 Alt a 10 Alt a 12
Alt a 13    
*International Union of Immunological Societies (www.allergen.org) Jan. 2008.


m229 rAlt a 1

Recombinant non-glycosylated protein produced in an E. coli strain carrying a cloned cDNA encoding Alternaria alternata allergen Alt a 1

 
Biological function: Unknown
Mw: 29-31 kDa

Allergen description

More than 9 allergens have been described in A. alternata extracts, although only 2 of them are major allergens. Alt a 1 is a dimer of 29 kDa that dissociates into 14.5 and 16 kDa subunits under reducing conditions (29). Studies indicate that this allergen may have several conformational or structural isoforms of this protein, which may be responsible for the allergen appearing to have a number of different molecular sizes (31,36).

Alt a 1 is recognised by approximately 80% to 100% of all Alternaria-allergic patients (29,55). rAlt a 1 has been shown to be similar to natural Alt a 1. In a study of A. alternata-sensitised individuals, 85.7% to >90% were shown to be sensitised to to rAlt a 1 (25,29). Similarly, in a study of patients with A. alternata allergy, sensitisation could be detected by means of skin test. No false-positive results were obtained with control patients, even at the highest concentration (14). Evaluation of recombinant Alt a 1 using skin test was positive in 6 of 7 individuals allergic to Alternaria. In contrast, in a study using commercially available A. alternata extracts, researchers failed to correctly diagnose Alternaria-allergic patients in 2/10 cases (25).


In a study of 42 patients allergic to A. alternata, 10 atopic patients were found to have no skin-reactivity for the A. alternata extract; commercial extracts were used for testing. However, all patients were shown to have skin-reactivity to A. alternata when purified allergens were used for testing. No false-positive reactions were detected. Analysis showed no IgE-binding differences between nAlt a 1 and rAlt a 1. Specific IgE levels to nAlt a 1 or rAlt a 1 showed significant correlation and similar sensitivity and specificity (14).
 
Compiled by Dr Harris Steinman, harris@zingsolutions.com

References

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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.