clear search
Search
Search Suggestions
Recent searches Clear History
Allergy & Autoimmune Disease
Allergy Solutions
ImmunoCAP Allergy Solutions
The gold standard in in-vitro allergy diagnostics with more than 500 whole allergens and allergen mixes.
Allergen Components
Food Allergies
Interpretation Guides
Respiratory Allergies
Product Catalog
Research & Customized Solutions
Specific IgE tests
Autoimmunity Solutions
EliA Autoimmunity Solutions
A high specificity and high sensitivity portfolio of more than 50 clinically relevant tests for autoimmune diseases.
Rheumatoid Arthritis
Connective Tissue Diseases
Celiac Disease
Thyroid Diseases
Vasculitis and Goodpasture Syndrome
Antiphospholipid Syndrome
Pernicious Anemia
Inflammatory Bowel Disease
Liver Diseases
Product Catalog
Polyautoimmunity
Systems
Phadia Laboratory Systems
Fully automated and scalable instruments to optimize allergy and autoimmune workflow.
Phadia 200
Phadia 250
Phadia 1000
Phadia 2500
Phadia 5000
Phadia Prime
Additional Services
Product Catalog
Resources
Center for Knowledge
Training, education, and service material for autoimmune and allergy testing.
All Resources
ImmunoSpotlight
Allergen Encyclopedia
Phadia Academy
Service & Support
Library
Lab Training
Thermo Fisher Scientific
visit thermofisher.com
Contact Us

Whole Allergen

m6 Alternaria alternata

m6 Alternaria alternata Scientific Information

Type:

Whole Allergen

Display Name:

Alternaria alternata

Route of Exposure:

Inhalation

Family:

Pleosporaceae

Species:

Alternaria alternata

Latin Name:

Alternaria tenuis

Related Allergens: m229 Alt a 1

Summary

Alternaria alternata (A. alternata) is a predominantly outdoor mold, but it can also be found indoors. A member of the Pleosporaceae family, the genus Alternaria comprises more than 270 species of dematiaceous (black) hyphomycetes. Geography, seasonality, atmospheric conditions and time of the day influence their distribution. A. alternata spores spread widely on dry, warm, and windy days and usually peak during summer and early autumn. They can also be found in soil. A. alternata is a cosmopolitan mold and one of the most frequent fungal sensitizers, with a sensitization prevalence varying from 0.2% to 14.4% across the globe. Inhalation of A. alternata spores is associated with upper and lower respiratory hypersensitivity, mainly asthma and allergic fungal rhinosinusitis. Allergic bronchopulmonary mycosis and hypersensitivity pneumonitis may also develop. Allergens of A. alternata are found in both conidia and mycelia. Twelve molecular allergens of A. alternata have been approved by the World Health Organization/International Union of Immunological Studies (WHO/IUIS) Allergen Nomenclature Sub-Committee (www.allergen.org, accessed Feb 3rd, 2021). Alt a 1 is a major allergen and a marker of genuine sensitization to A. alternata. Sensitization to A. alternata is often associated with sensitization to other molds and to other airborne allergenic sources such as pollens and mites. Co-sensitization and cross-reactivity to some food allergens have also been reported.

Allergen

Nature

Alternaria is a huge, complex genus comprising characteristic dematiaceous hyphomycetes. They mainly consist of saprotrophs and plant pathogens (1-3). A. alternata is regarded as one of the common species of this genus and its fungal spores are found all-round the year, predominantly outdoors (2, 3).

A. alternata grows fast in colonies of dark color ranging from gray, olive to olive brown. They have dark-colored hyphae divided by septa and forming septate conidiospores (3). The conidia (spores) are medium brown with short, cylindrical beaks, forming long and profusely branched-chain structures (1, 3).

Habitat

A. alternata is a prominent outdoor mold found ubiquitously in various environments all over the globe. The saprotroph species are mostly found in the soil, plants, and foodstuffs and parasitic species are present in animals, humans, and plants (2, 3).

The fungal spores are airborne and usually disperse when the weather becomes dry, warm, and windy. They achieve their peak levels in late summer to fall while absent in winters. The spores can survive at 2-32℃ temperatures with the optimum being 20°C (2, 3).

A. alternata is also found in indoor environments, particularly in damp, water-damaged buildings, and is one of the molds associated with the “sick building syndrome”. Moreover, they can be found in textiles (carpets or beddings) and bed dust samples (3).

Taxonomy

Alternaria is a complex and morphologically diverse genus. The Alternaria taxa have been classified based on either the size of conidia or host specificity. There are more than 270 species in the genus Alternaria. A. alternata is the most common species of this genus (1-3).

The taxonomic tree of A. alternata is as given in the table (2-4) as accessed on February 11, 2021:

Taxonomic tree of A. alternata (2-4)
Domain Eukaryota
Kingdom Fungi
Phylum Ascomycota
Class Dothideomycetes (Euascomycetes)
Order Pleosporales
Family Pleosporaceae
Genus Alternaria
Species A. alternata
Taxonomic tree of A. alternata (2-4)

Tissue

Allergens of A. alternata are found in both conidia and mycelia. The hyphae that make up the mycelia are brown and septate. The conidia are simple, large, measuring 45-50×36 μm and, occur either singly or in the form of chains. Conidia are typically large, uniform with extended tips. However, if grown in cool and dry conditions, tips are shorter. Spores are released from the conidiophores in dry air passively and also by strong wind gusts (3). 

Epidemiology

Worldwide distribution

While the true prevalence of A. alternata sensitization is unknown and the recorded prevalence of Alternaria immunoglobulin (IgE) reactivity in humans varies widely, it is reported to induce potent respiratory allergic reactions such as rhinitis, asthma, dermatitis, and human infections (5).

The European Community Respiratory Health Survey (ECRHS) I (2000-2002) studied 11,355 members of the general adult population for allergies caused by common allergens through skin prick tests (SPT) and specific IgE testing. The study, across 37 centers in 17 countries, including Australia, the United States of America (USA), the United Kingdom (UK), and Iceland, reported a 4.4% prevalence of sensitization to A. alternata allergens, varying from 0.2% to 14.4% in various centers (6, 7).

A multi-center, open-label study by the Global Asthma and Allergy European Network (GA2LEN) assessed clinically relevant sensitization rates of several allergens in 14 European countries. It involved 3,034 individuals suspected of having allergic diseases including allergic rhinitis (AR), asthma, atopic dermatitis (AD), and food allergies. The clinically relevant sensitization rate of A. alternata across Europe was found to be 6.1%, again with wide geographical variations: 0.0% (UK), 1.5% (Finland). 2.6% (Austria), 3.0% (Italy), 3.5% (Poland), 4.1% (Switzerland), 4.2% (France), 4.9% (Belgium), 5.5% (The Netherlands), 7.3% (Portugal), 7.9% (Germany), 8.2% (Denmark), 10.4% (Hungary) to as high as 18.7% (Greece) (8). A study conducted in Austria among 4,962 allergic patients with respiratory symptoms (rhinitis and asthma) found A. alternata sensitization in 12.6% (410/3248) allergic patients based on positive SPT to at least one allergenic source and in 66.1% (410/621) fungi-allergic patients (9). Another study in Finland found a 2.8% prevalence of IgE-mediated sensitization to A. alternata among 1,504 allergic patients (10).

Furthermore, a cross-sectional study among 1006 allergic patients in Iran reported sensitization to Alternaria to be 5.3% based on SPT reactivity (11). In the Guangdong province of China, sensitization to A. alternata among asthmatic children was found to be 14.9% (59/397) while among patients with AR it reached 44.9% (730/1625) (12). 

Risk factors

Individuals working on farms and in sawmills are at a high risk of allergic reactions and infections induced by A. alternata due to the high level of its allergen count in these environments. Also, among people with respiratory allergy, younger individuals are at greater risk of developing sensitization to A. alternata than elderly people (5). Immune suppression is a risk factor for fungal opportunistic infections including alternariosis (1).

Environmental Characteristics

Worldwide distribution

Alternaria is one of the most common fungi in the world (13). The distribution of A. alternata is highly affected by geographical location, season, atmospheric conditions, and time of the day (5). It usually occurs in warm climates and tropical and sub-tropical zones, with spore counts remaining high throughout the year, while in temperate climates, the spores mainly occur from May to November (3). It is known to be present worldwide, in Asia especially China, Europe, the USA, Australia, and New Zealand (12, 14), while data from African countries are scarce (15).

Route of Exposure

Main

A. alternata fungal spores can enter the upper and lower respiratory tract through inhalation (5, 16).  

Clinical Relevance

A. alternata has been identified as one of the major allergenic sources for the development and severity of respiratory allergic diseases. The allergenic threshold count of Alternaria spores (100 spores/m3) in the air is anticipated to be low as compared to Cladosporium spores (3000 spores/m3). Severe respiratory allergic symptoms, hospital admissions, and deaths due to asthma were found to be directly proportional to the levels of fungal spores in the atmosphere (5).

Allergic rhinitis

Sensitization to Alternaria species (spp.) is considered to be associated with the development of AR in children (17). However, it is not found to be associated with severity of AR as demonstrated in two studies conducted in Iran (18, 19). The first case control study reported the overall prevalence of sensitization to Alternaria spp. (positive SPT reactivity) to be 32.8% of the 58 AR patients with 45.5% having mild AR and 58.3% having moderate to severe. The study also reported that Alternaria sensitization was significantly associated (p<0.018) with the presence of Alternaria fungi in the nasal cavity of patients with AR (19). The second study conducted among 567 AR patients also found that severity of asthma was not significantly different (p=0.2) among intermittent AR (14.2%) or persistent AR (85.8%) patients sensitized to A. alternata (18).

Sensitization to A. alternata (positive SPT or IgE) in mold allergic patients (89-90%) conveys greater risk for development of asthma and intermittent AR than other molds, as reported in a study conducted in 239 mold allergic patients (20).

The prevalence of A. alternata sensitization (positive SPT reactivity) in AR shows wide geographical variation. It was reported to be 10-15% among AR patients (n=656) in Southwestern Iran (21) and 5.72% (n=699) in Northeastern Iran (11). Further, AR and allergic rhino-conjunctivitis were observed in 27.5% and 17.5% of 40 Finnish patients sensitized to A. alternata or C. herbarum (10). Looking into the Asian prevalence, Alternaria spp. sensitization was reported to be 17.6% in Malaysia (Malay, Chinese and Indian ethnicity) among 85 adult patients (age> 15 years) with AR (22) while prevalence in India was found to be only 2.6% among 4263 patients (age: 2-82 years) with AR and asthma (23). Similar prevalence (0-5%) was reported in Nepal in a cross-sectional study among 170 AR patients (age: 18-66 years) (24).

Interestingly, Alternaria spp. is also related to another phenotype of AR known as local allergic rhinitis (LAR), often in the Mediterranean areas. LAR is confirmed usually based on nasal production of specific IgE without any systemic sensitization (25). The role of Alternaria spp. in LAR was demonstrated in two studies. The first one was conducted on 56 children with AR, of whom, 37.5% were sensitized to Alternaria based on positive SPT while 80.3% of children were found positive for nasal IgE test to Alternaria spp. A nasal provocation test was performed to establish the relationship of Alternaria spp. with LAR and was found to be significant in patients with positive nasal IgE than in patients with positive SPT (26). Further, the second prospective study conducted on 84 adult patients with LAR found Alternaria spp. sensitization in 3.6% of patients (27).

Asthma

Sensitization to A. alternata is frequent in asthmatic patients (28). Its clinical relevance resides in its association with the severity of asthma (14, 29, 30)  and the occurrence of exacerbations (30). Indeed, sensitization to A. alternata is considered to be a significant risk factor [Odds ratio (OR) – 2.03, 95% Confidence Interval (CI), p<0.001] for severe asthma (especially asthma attacks following storms, termed thunderstorm-asthma) as found in the ECRHS in European countries, US and Australia/New Zealand (5, 14).

Its overall prevalence was 11.9% among 1132 asthmatic patients across the globe in a multicenter cross-sectional epidemiological survey (ECRHS). The proportions of participants with asthma showing sensitization to A. alternata varied among study sites, from 28.2% (Portland, US), 17.6% (UK and Ireland), 13.7% (Central Europe), 10.5% (Australia and New Zealand), 10.2% (Northern Europe) to 4.7% (Southern Europe) (14). In a cohort study of 656 patients with asthma, AR or AD in Iran, sensitization to Alternaria spp. was reported in ~15% of patients with asthma (21). However, stratification as mild, moderate and severe persistent asthma in another study conducted with 187 patients found SPT reactivity to A. alternata in 34.2%, 51.9% and 13.9% respectively, without a significant difference (18).

Tariq et al. (1996) addressed fungal sensitization in an Isle of Wight birth cohort of 981 children (4-year-old) at risk for atopic disease. Of these, 6% reacted to A. alternata. In this study, typical outdoor molds  A. alternata and C. herbarum were the third most common cause of sensitization, after house dust mite and pollens (31).

Taking it the other way, asthma was observed in 16 out of 40 Finnish patients showing positive SPT to A. alternata or C. herbarum (10). Furthermore. an Australian prospective cohort study involving 399 school children with positive SPT to one or more aeroallergens found significantly increased airway responsiveness in children sensitized to Alternaria as compared to other allergens. This study suggested that sensitized patients in areas with a high spore count of Alternaria can develop severe asthmatic reactions (13). asdad

Atopic Dermatitis

Similar to AR, the prevalence of sensitization to A. alternata in AD patients shows important variations as a function of the environment and the study population. In a study in Finland, AD was observed in 58% of 40 patients showing positive SPT to A. alternata or C. herbarum (10). Another study among 60 AD patients in Czech republic reported sensitization to fungal allergens in 35 patients, of which 13 (22% of the study population) were sensitized to A. alternata allergens Alt a 1 and Alt a 6 (32).

Wide geographical variation was also observed in the prevalence of A. alternata sensitization (positive SPT or IgE reactivity) among AD patients in Iran. Sensitization rates varied from 32% in northern regions to around 3% in the South (33). (21). (34). (35). Such discrepancy may also be related to the demographic and clinical features of the study populations.

Other diseases

Alternaria mycotoxins such as alternariol are contaminants of cereals, fruit, and fermented foods  (3).

Infections

A. alternata can cause human infections such as cutaneous and subcutaneous infections, oculomycosis, sinusitis, onychomycosis, and invasive diseases (36).

Hypersensitivity pneumonitis (HP)

HP is an immune-mediated interstitial lung disease, either acute or chronic, developing in genetically predisposed individuals experiencing prolonged exposure to certain organic or inorganic inhaled antigens (37). Molds such as A. alternata, Aspergillus, Cladosporium, Mucor, etc. are common causative agents of HP. A. alternata is mostly involved in occupational HP, typically as humidifier lung disease or woodworker’s lung disease (38). Other occupational sources of exposure to A. alternata followed by occupational PHS are more anecdotal, such as in shiitake mushroom farmers (39). The diagnosis of PHS requires thorough documentation of clinical and radiological features, home and occupational exposure, followed by determination of specific IgG (current test replacing the 20th century “precipitins”) directed to the culprits (40). Elevated levels of IgG (not IgE) to A. alternata upon diagnostic work-up, decreasing as a result of antigen avoidance, e.g., during the patient’s holidays, support the diagnosis of PHS caused by this mold (40).

Allergic bronchopulmonary mycosis (ABPM)

A. alternata is an uncommon cause of ABPM, estimated as less than 1% in Aspergillus-unrelated cases of ABPM (41). Two cases of ABPM due to Alternaria are reported in the literature: a 21-year-old male from the UK with a history of atopy and exacerbation of asthma symptoms (42), and an immunocompromised patient from India (28).

Prevention and Therapy

Prevention strategies

Avoidance

A. alternata is difficult to avoid as it is predominantly detected outdoors. Therefore, patients sensitized to fungi are advised to avoid areas with high allergen/spore counts, use masks when outside, and follow appropriate therapy (5). However, Alternaria allergen concentrations can also be high indoors, requiring the implementation of general measures aiming at mold reduction. The dampness in the environment can be avoided or decreased by frequently checking the intrusion, condensation and leakage of water in homes. Contaminated non-porous surfaces can be cleaned regularly with soap-water solutions or with bleach. Limited use of humidifiers or cool mist, frequent cleaning of the carpets and air purifiers, and regular maintenance of ventilation systems, humidifiers and similar devices could also help lower the mold concentrations in the indoor environments (43). 

Molecular Aspects

Allergenic molecules

Currently, 17 allergens of A. alternata have been recognized, 12 of which are officially listed in the database of the World Health Organization/International Union of Immunological Studies (WHO/IUIS) Allergen Nomenclature Sub-Committee (3, 5, 44).

The table below provides detailed information on each of the allergenic protein identified by WHO/IUIS as on February 11, 2021:

Allergens Molecular Weight (kDa) Biochemical name Allergenicity
Alt a 1 16.4 kDa and 15.3 kDa (30 kDa non-red) (dimer)  
  • Major allergen and a marker of genuine sensitization to A.  alternata (5).
  • IgE reactivity prevalence of 80% and 98% in 98 and 42 A. alternata sensitized patients are reported respectively (45, 46).
  • Both IgE and IgG antibodies found in asthma/rhinitis and atopic dermatitis patients were found to be 93% and 47% respectively (47).
  • Involved in spore germination (5).
Alt a 3 70 Heat shock protein
  • Minor allergen (5).
  • Recognized by 5% of the 7 sera of atopic patients sensitized to A. alternata (48).
Alt a 4 57 Disulfide isomerase
  • Minor allergen (5).
  • Positive immunoblot recognition by 42% of 98 A. alternata sensitized patients. (45).
Alt a 5 11 Ribosomal protein P2
  • Minor allergen (5).
  • Previously known as Alt a 6.
  • Recognized by 14% of the 7 sera of atopic patients sensitized to A. alternata (48).
Alt a 6 45 Enolase
  • Minor allergen (5).
  • Previously known as Alt a 5 or Alt a 11.
  • Recognized by 22% of the 23 sera of patients sensitized to A. alternata (49).
Alt a 7 22 YCP4 protein
  • Minor allergen (5).
  • Positive immunoblot recognition by 7% of 98 A. alternata sensitized patients (45).
Alt a 8 29 Mannitol dehydrogenase enzyme
  • Minor allergen (5).
  • IgE reactivity on immunoblots was found to be 41% in 22 A. alternata allergic patients (50).
Alt a 10 53 Aldehyde dehydrogenase
  • Minor allergen (5).
  • Positive immunoblot recognition by 2% of 98 A. alternata sensitized patients (45).
Alt a 12 11 Acid ribosomal protein P1
  • Minor allergen (5).
Alt a 13 26 Glutathione-S-transferase enzyme
  • Minor allergen (5).
  • Positive skin test in 82% of 17 A. alternata sensitized patients (51)
Alt a 14 24 Manganese superoxide dismutase
  • Minor allergen (5).
  • Positive immunoblot recognition by 11.5% of 61 A. alternata sensitized patients (52).
  • Sensitization may be associated with allergic bronchopulmonary mycosis (5).
Alt a 15 58 Serine protease
  • Minor allergen (5).
  • Positive immunoblot recognition by 10.2% of 59 A. alternata sensitized patients (53).
  • Mostly observed in polysensitized individuals (5).
Allergens Molecular Weight (kDa) Biochemical name Allergenicity

kDa: kilodaltons, IgE: Immunoglobulin E, YCP: Yeast Centromere Plasmids

Five other A. alternata allergens have been reported but have not yet been included in the WHO/IUIS approved list as of Feb 3rd, 2021. These include Alt a TCTP (translationally controlled tumor protein), Alt a NTF2 (nuclear transport factor 2), Alt a 2, Alt a 9 and Alt a 70 kDa. The reported IgE reactivity of Alt a TCTP, Alt a NTF2, Alt a 2 and Alt a 9 in different studies was found as 4% (n=16), 0.8% (n=480), 0.0% (n=42) and 5% (n=98) respectively in A. alternata sensitized patients. Alt a 70 kDa triggered skin reactivity in 87% (n=16) of A. alternata sensitized individuals (5).

Biomarkers of severity

Alt a 1, recognized as a major A. alternata allergen and one of the primary elicitors of airborne allergies, is also considered a marker of genuine sensitization to A. alternata. It is specific for Alternaria genus and its related taxa like Pleosporaceae family species which has reported the presence of homologs of Alt a 1 (5). Further, Alt a 1 is found to be the protein that is formed before the germination of spores and related to the pathogenicity of the fungi (54). Alt a 1 level estimation in the environment could be used as a marker to predict the risk of development of respiratory reactions in patients allergic to A. alternata (55).

Furthermore, sensitization to other allergens like Alt a 3, Alt a 6, Alt a 10, and Alt a 13 may indicate co-sensitization as well as cross-reactivity with other allergens (3). Alt a 6 sensitization may be associated with cross-reactivity among members of different phyla like food, grass pollen and latex allergens (3, 32).  

Cross-reactivity

Cross-reactivity is linked to the homology between allergens found in A. alternata and other allergenic molds, mainly Cladosporium, Penicillium, and Aspergillus. Less frequent cross-reactivity has been reported with foods: mushrooms and spinach (5).

Clinical cross-reactivity can occur without molecular homology, as reported for A. alternata and kiwifruit. Alt a 1 interacts with the thaumatin-like protein (PR-5) Act d 2 present in the pulp of kiwifruit and may be responsible for reactions to A. alternata caused by kiwifruit ingestion (54).

The table below provides the list of most common cross-reactive A. alternata allergens with other fungal allergens (5): 

A. alternata allergen Fungal Homologs IUIS allergens Cross-reactive species
Alt a 3

Pen c 19

Mala s 10

Penicillium citrinum

Malassezia sympodialis
Alt a 5

Fus c 1

Cla h 5

Asp f 8

Fusarium culmorum

Cladosporium herbarum

Aspergillus fumigatus
Alt a 6

Cla h 6

Asp f 22

Pen c 22

Cur l 2

Rho m 1

Fusarium culmorum

Cladosporium herbarum

Penicillium citrinum

Curvularia lunata

Rhodotorula mucilaginosa
Alt a 7

Cla h 7

Cladosporium herbarum
Alt a  8

Cla h 8

Cladosporium herbarum
Alt a 10 Cla h 10 Cladosporium herbarum
Alt a 12

Cla h 12

Pen cr 26

Pen b 26

Cladosporium herbarum

Penicillium crustosum

Penicillium brevicompactum
Alt a 14

Asp f 6

Mala s 11

Aspergillus fumigatus

Malassezia sympodialis
Alt a 15

Cur l 4

Cla h 9

Cla c 9

Asp f 18, Asp f 13

Asp v 13

Asp o 13

Asp fl 13

Pen ch 13, Pen ch 18

Pen c 13

Rho h 2

Tri r 2

Curvularia lunata

Cladosporium herbarum

Cladosporium cladosporioides

Aspergillus fumigatus

Aspergillus versicolor

Aspergillus oryzae

Aspergillus flavus

Penicillium chrysogenum

Penicillium citrinum

Rhodotorula mucilaginosa

Trichophyton rubrum
A. alternata allergen Fungal Homologs IUIS allergens Cross-reactive species

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Christian Fischer

 

Last reviewed: March 2021

References
  1. Pastor FJ, Guarro J. Alternaria infections: laboratory diagnosis and relevant clinical features. Clin Microbiol Infect. 2008;14(8):734-46.
  2. Levetin E, Horner WE, Scott JA, Environmental Allergens W. Taxonomy of Allergenic Fungi. J Allergy Clin Immunol Pract. 2016;4(3):375-85 e1.
  3. Kustrzeba-Wojcicka I, Siwak E, Terlecki G, Wolanczyk-Medrala A, Medrala W. Alternaria alternata and its allergens: a comprehensive review. Clin Rev Allergy Immunol. 2014;47(3):354-65.
  4. CABI. Alternaria Alternata: CAB International; 2021 [updated January 15, 2021; cited 2021 February 11, 2021]. Available from: https://www.cabi.org/isc/datasheet/4480#totaxonomicTree.
  5. Gabriel MF, Postigo I, Tomaz CT, Martinez J. Alternaria alternata allergens: Markers of exposure, phylogeny and risk of fungi-induced respiratory allergy. Environ Int. 2016a;89-90:71-80.
  6. Bousquet PJ, Hooper R, Kogevinas M, Jarvis D, Burney P. Number of allergens to be tested to assess allergenic sensitization in epidemiologic studies: results of the European Community Respiratory Health Survey I. Clinical & Experimental Allergy. 2007;37(5):780-7.
  7. Bousquet PJ, Chinn S, Janson C, Kogevinas M, Burney P, Jarvis D. Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European Community Respiratory Health Survey I. Allergy. 2007;62(3):301-9.
  8. Burbach GJ, Heinzerling LM, Edenharter G, Bachert C, Bindslev‐Jensen C, Bonini S, et al. GA2LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe. Allergy. 2009;64(10):1507-15.
  9. Mari A, Schneider P, Wally V, Breitenbach M, Simon-Nobbe B. Sensitization to fungi: epidemiology, comparative skin tests, and IgE reactivity of fungal extracts. Clin Exp Allergy. 2003;33(10):1429-38.
  10. Reijula K, Leino M, Mussalo-Rauhamaa H, Nikulin M, Alenius H, Mikkola J, et al. IgE-mediated allergy to fungal allergens in Finland with special reference toAlternaria alternata and Cladosporium herbarum. Annals of Allergy, Asthma & Immunology. 2003;91(3):280-7.
  11. Mahboubi Oskouei Y, Farid Hosseini R, Ahanchian H, Jarahi L, Ariaee N, Jabbari Azad F. Report of Common Aeroallergens among Allergic Patients in Northeastern Iran. Iranian journal of otorhinolaryngology. 2017;29(91):89-94.
  12. Guan K, Liu B, Wang M, Li Z, Chang C, Cui L, et al. Principles of Allergen Immunotherapy and Its Clinical Application in China: Contrasts and Comparisons with the USA. Clinical reviews in allergy & immunology. 2019;57(1):128-43.
  13. Downs SH, Mitakakis TZ, Marks GB, Car NG, Belousova EG, Leüppi JD, et al. Clinical importance of Alternaria exposure in children. Am J Respir Crit Care Med. 2001;164(3):455-9.
  14. Zureik M, Neukirch C, Leynaert B, Liard R, Bousquet J, Neukirch F. Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey. Bmj. 2002;325(7361):411.
  15. Pefura-Yone EW, Mbele-Onana CL, Balkissou AD, Kenmegne-Noumsi EC, Boulleys-Nana JR, Kolontchang-Yomi BL, et al. Perennial aeroallergens sensitisation and risk of asthma in African children and adolescents: a case-control study. The Journal of asthma : official journal of the Association for the Care of Asthma. 2015;52(6):571-5.
  16. Shin SH, Ponikau JU, Sherris DA, Congdon D, Frigas E, Homburger HA, et al. Chronic rhinosinusitis: an enhanced immune response to ubiquitous airborne fungi. J Allergy Clin Immunol. 2004;114(6):1369-75.
  17. Nazari Z, Ghaffari J, Ghaffari N, Ahangarkani F. A review on hypersensitivity reactions to fungal aeroallergens in patients with allergic disorders in Iran. Current medical mycology. 2019;5(1):42-7.
  18. Farrokhi S, Gheybi MK, Movahed A, Tahmasebi R, Iranpour D, Fatemi A, et al. Common aeroallergens in patients with asthma and allergic rhinitis living in southwestern part of Iran: based on skin prick test reactivity. Iranian journal of allergy, asthma, and immunology. 2015;14(2):133-8.
  19. Mokhtari Amirmajdi M, Mokhtari Amirmajdi NA, Eftekharzadeh Mashhadi I, Jabari Azad F, Tavakol Afshari J, Shakeri MT. Alternaria in patients with allergic rhinitis. Iranian journal of allergy, asthma, and immunology. 2011;10(3):221-6.
  20. Kołodziejczyk K, Bozek A. Clinical Distinctness of Allergic Rhinitis in Patients with Allergy to Molds. BioMed Research International. 2016;2016:3171594.
  21. Moghtaderi M, Hejrati Z, Kolahi N, Heidari B. Sensitization to aeroallergens in patients with allergic rhinitis, asthma, and atopic dermatitis in Shiraz, Southwestern Iran. 2015;29(2):79-83.
  22. Wan Ishlah L, Gendeh BS. Skin prick test reactivity to common airborne pollens and molds in allergic rhinitis patients. The Medical journal of Malaysia. 2005;60(2):194-200.
  23. Kumar R, Kumar M, Bisht I, Singh K. Prevalence of aeroallergens in patients of bronchial asthma and/or allergic rhinitis in India based on skin prick test reactivity. 2017;31(2):45-55.
  24. Pokharel M, Shrestha BL, Karn D, Dhakal A, K.C AK, Shrestha KS, et al. Prevalence of Aeroallergens in Allergic Rhinitis in a Tertiary Care Hospital. JNMA J Nepal Med Assoc. 2020;58(231):866-70.
  25. Eguiluz-Gracia I, Pérez-Sánchez N, Bogas G, Campo P, Rondón C. How to Diagnose and Treat Local Allergic Rhinitis: A Challenge for Clinicians. Journal of clinical medicine. 2019;8(7).
  26. Fuiano N, Fusilli S, Incorvaia C. A role for measurement of nasal IgE antibodies in diagnosis of Alternaria-induced rhinitis in children. Allergologia et immunopathologia. 2012;40(2):71-4.
  27. Krajewska-Wojtys A, Jarzab J, Zawadzińska K, Pyrkosz K, Bozek A. Local Allergic Rhinitis in Adult Patients with Chronic Nasal Symptoms. International archives of allergy and immunology. 2017;173(3):165-70.
  28. Chowdhary A, Agarwal K, Randhawa HS, Kathuria S, Gaur SN, Najafzadeh MJ, et al. A rare case of allergic bronchopulmonary mycosis caused by Alternaria alternata. Med Mycol. 2012;50(8):890-6.
  29. Peat JK, Tovey E, Mellis CM, Leeder SR, Woolcock AJ. Importance of house dust mite and Alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia. 1993;23(10):812-20.
  30. Fukutomi Y, Taniguchi M. Sensitization to fungal allergens: Resolved and unresolved issues. Allergology International. 2015;64(4):321-31.
  31. Tariq S, Matthews S, Stevens M, Hakim E. Sensitization to Alternaria and Cladosporium by the age of 4 years. Clinical & Experimental Allergy. 1996;26(7):794-8.
  32. Čelakovská J, Bukač J, Vaňková R, Krcmova I, Krejsek J, Andrýs C. Sensitisation to molecular allergens of Alternaria alternata, Cladosporium herbarum, Aspergillus fumigatus in atopic dermatitis patients. Food and Agricultural Immunology. 2019;30(1):1097-111.
  33. Hedayati MT, Arabzadehmoghadam A, Hajheydari Z. Specific IgE against Alternaria alternata in atopic dermatitis and asthma patients. European review for medical and pharmacological sciences. 2009;13(3):187-91.
  34. Bonyadi MR, Hassanzadeh D, Seyfizadeh N, Borzoueisileh S. Assessment of allergen-specific IgE by immunoblotting method in atopic dermatitis. European annals of allergy and clinical immunology. 2017;49(5):213-9.
  35. Ghaderi R, Rashavi M. Prevalence of common allergens among patients with atopic dermatitis in Eastern Iran. MOJ Immunol. 2018;6(3):74-80.
  36. Jain A, Waindeskar V, Nema M. Innovative management of difficult paediatric airway, using antegrade seldinger technique. 2015;33(4):599-600.
  37. Costabel U, Miyazaki Y, Pardo A, Koschel D, Bonella F, Spagnolo P, et al. Hypersensitivity pneumonitis. Nature reviews Disease primers. 2020;6(1):65.
  38. Nogueira R, Melo N, Novais EBH, Martins N, Delgado L, Morais A, et al. Hypersensitivity pneumonitis: Antigen diversity and disease implications. Pulmonology. 2019;25(2):97-108.
  39. Ampere A, Delhaes L, Soots J, Bart F, Wallaert B. Hypersensitivity pneumonitis induced by Shiitake mushroom spores. Med Mycol. 2012;50(6):654-7.
  40. Quirce S, Vandenplas O, Campo P, Cruz MJ, de Blay F, Koschel D, et al. Occupational hypersensitivity pneumonitis: an EAACI position paper. Allergy. 2016;71(6):765-79.
  41. Chowdhary A, Agarwal K, Kathuria S, Gaur SN, Randhawa HS, Meis JF. Allergic bronchopulmonary mycosis due to fungi other than Aspergillus: a global overview. Critical reviews in microbiology. 2014;40(1):30-48.
  42. Singh B, Denning DW. Allergic bronchopulmonary mycosis due to Alternaria: Case report and review. Med Mycol Case Rep. 2012;1(1):20-3.
  43. Portnoy JM, Jara D. Mold allergy revisited. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2015;114(2):83-9.
  44. WHO/IUIS. Alternaria Alternata: WHO/IUIS Allergen Nomenclature Subcommittee; 2019 [updated June 28, 2019; cited 2021 February 11, 2021]. Available from: http://www.allergen.org/search.php?allergensource=Alternaria+alternata.
  45. Achatz G, Oberkofler H, Lechenauer E, Simon B, Unger A, Kandler D, et al. Molecular cloning of major and minor allergens of Alternaria alternata and Cladosporium herbarum. Mol Immunol. 1995;32(3):213-27.
  46. Asturias JA, Ibarrola I, Ferrer A, Andreu C, Lopez-Pascual E, Quiralte J, et al. Diagnosis of Alternaria alternata sensitization with natural and recombinant Alt a 1 allergens. J Allergy Clin Immunol. 2005;115(6):1210-7.
  47. Vailes LD, Perzanowski MS, Wheatley LM, Platts-Mills TA, Chapman MD. IgE and IgG antibody responses to recombinant Alt a 1 as a marker of sensitization to Alternaria in asthma and atopic dermatitis. Clin Exp Allergy. 2001;31(12):1891-5.
  48. De Vouge MW, Thaker AJ, Zhang L, Muradia G, Rode H, Vijay HM. Molecular cloning of IgE-binding fragments of Alternaria alternata allergens. International archives of allergy and immunology. 1998;116(4):261-8.
  49. Simon-Nobbe B, Probst G, Kajava AV, Oberkofler H, Susani M, Crameri R, et al. IgE-binding epitopes of enolases, a class of highly conserved fungal allergens. J Allergy Clin Immunol. 2000;106(5):887-95.
  50. Schneider PB, Denk U, Breitenbach M, Richter K, Schmid-Grendelmeier P, Nobbe S, et al. Alternaria alternata NADP-dependent mannitol dehydrogenase is an important fungal allergen. Clin Exp Allergy. 2006;36(12):1513-24.
  51. Shankar J, Singh BP, Gaur SN, Arora N. Recombinant glutathione-S-transferase a major allergen from Alternaria alternata for clinical use in allergy patients. Mol Immunol. 2006;43(12):1927-32.
  52. Gabriel MF, Postigo I, Gutierrez-Rodriguez A, Sunen E, Guisantes J, Tomaz CT, et al. Characterisation of Alternaria alternata manganese-dependent superoxide dismutase, a cross-reactive allergen homologue to Asp f 6. Immunobiology. 2015;220(7):851-8.
  53. Gabriel MF, Postigo I, Gutierrez-Rodriguez A, Sunen E, Guisantes JA, Fernandez J, et al. Alt a 15 is a new cross-reactive minor allergen of Alternaria alternata. Immunobiology. 2016b;221(2):153-60.
  54. Gómez-Casado C, Murua-García A, Garrido-Arandia M, González-Melendi P, Sánchez-Monge R, Barber D, et al. Alt a 1 from Alternaria interacts with PR5 thaumatin-like proteins. FEBS Letters. 2014;588(9):1501-8.
  55. Feo Brito F, Alonso AM, Carnés J, Martín-Martín R, Fernández-Caldas E, Galindo PA, et al. Correlation between Alt a 1 levels and clinical symptoms in Alternaria alternata-monosensitized patients. Journal of investigational allergology & clinical immunology. 2012;22(3):154-9.