Optimal Aspergillus fumigatus and Asp f 1 serum IgG cut-offs for the diagnosis of allergic bronchopulmonary aspergillosis

ABSTRACT Allergic bronchopulmonary aspergillosis (ABPA) is an immunologically complex allergic disorder caused by the fungal pathogen Aspergillus fumigatus. Elevated levels of total immunoglobulin E (IgE), specific IgE, and IgG antibodies in sera are important immunodiagnostic criteria for ABPA. International reference standards or standardized immunodiagnostic assays are not available due to a lack of well-defined diagnostic antigens. The present study was carried out to identify and evaluate the immunodiagnostic relevance of synthetic epitopic peptides of Asp f 1, a major allergen, antigen, or cytotoxin of A. fumigatus. Five overlapping peptides were synthesized from the N terminus of Asp f 1, one of the potential immunodominant regions predicted by algorithmic programs. The 11-amino-acid synthetic peptide (P1) significantly inhibited both IgG binding (89.10% ± 4.45%) and IgE binding (77.32% ± 3.38%) of the standardized diagnostic antigen (SDA) (a well-defined pool of diagnostically relevant allergens and antigens of A. fumigatus). With a panel of sera of ABPA patients, allergic patients with skin test negativity to A. fumigatus, and healthy individuals, P1 showed a higher diagnostic efficiency than SDA (specific IgG, 100%; specific IgE, 98.3%). The diagnostic efficiency of P1 could be attributed to the presence of homologous epitopes in various immunodominant allergens or antigens of A. fumigatus. The ability of P1 to induce histamine release from sensitized mast cells and a Th2 type of cytokine profile in peripheral blood mononuclear cells of ABPA patients suggests its potential for use in intradermal testing. P1 could be further explored for development of a standardized, specific, and sensitive immunodiagnostic test for aspergillosis.

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Molecular allergen sensitization of Aspergillus fumigatus in allergic bronchopulmonary aspergillosis in Guangzhou, Southern China

10.21203/rs.3.rs-16458/v1 ◽

2020 ◽

Author(s):

Wenting Luo ◽

Haisheng Hu ◽

Zehong Wu ◽

Nili Wei ◽

Huimin Huang ◽

...

Keyword(s):

Aspergillus Fumigatus ◽

Southern China ◽

Allergic Bronchopulmonary Aspergillosis ◽

Strongly Correlated ◽

Guangzhou City ◽

Allergen Components ◽

Sige Level ◽

Asthma Patients ◽

Asp F 1 ◽

Fungal Allergen

Abstract Background Few studies have assessed the sensitization of mycotic allergens and Aspergillus fumigatus molecular allergen. This study aimed to investigate the connection between A.fumigatus components and mycotic allergens between allergic bronchopulmonary aspergillosis (ABPA) patients and A. fumigatus (Af)-sensitized asthma. Methods Serum Penicillium chrysogenum , Cladosporium herbarum , Mucor racemosus , Candida albicans , Alternaria alternata , Helminthosporium halodes and A.fumigatus allergen components (Asp f 1, Asp f 2, Asp f 3, Asp f 4, and Asp f 6) sIgE level were measured via ImmunoCAP assay in 18 ABPA patients and 54 Af-sensitized asthma patients in Guangzhou city. Results 94.44% of ABPA patients and 87.04% of Af-sensitized asthma patients were co-sensitization to at least one another fungal allergen. The positivity rates of C. albicans ( P < 0.05) and A.alternata ( P < 0.05) were higher in ABPA than that in Af-sensitized asthma patients. The positive rates of Asp f 1 (88.89% vs 59.26%, P < 0.05), Asp f 2 (66.67% vs 33.33%, P < 0.05), Asp f 4 (61.11% vs 33.33%, P < 0.05), and Asp f 6 (66.67% vs 14.81%, P < 0.001) in ABPA were higher than those in Af-sensitized asthma patients. Patients with ABPA had higher IgE levels of Asp f 1 ( P < 0.05), Asp f 4 ( P < 0.05) and Asp f 6 ( P < 0.001) than those of Af-sensitized asthma patients. A.fumigatus was strongly correlated with C.herbarum ( r s = 0.688) in ABPA and A.alternata ( r s = 0.692) in Af-sensitized asthma patients. Optimal scale analysis was show that ABPA was more relevant to Af-components. (Cronbach`s alpha = 90.7%) Conclusion The A.fumigatus components and it`s connection with various mycotic allergens were different in ABPA and Af-sensitized asthma patients. This findings can expected to help local doctors in the diagnosis and immunotherapy of fungal allergies.

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Medical algorithm: Aspergillus fumigatus components in the diagnosis of Allergic Bronchopulmonary Aspergillosis

Allergy ◽

10.1111/all.15001 ◽

2021 ◽

Author(s):

R. Lukaszewicz ◽

G. Mahay ◽

O. Boyer ◽

J. Martinet

Keyword(s):

Aspergillus Fumigatus ◽

Allergic Bronchopulmonary Aspergillosis

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Aspergillus fumigatus. [Descriptions of Fungi and Bacteria].

IMI Descriptions of Fungi and Bacteria ◽

10.1079/dfb/20056400092 ◽

1966 ◽

Author(s):

A. H. S. Onions

Keyword(s):

Aspergillus Fumigatus ◽

Geographical Distribution ◽

Disease Incidence ◽

Allergic Bronchopulmonary Aspergillosis ◽

Wild Birds ◽

Mastoid Cavity ◽

Chronic Infections ◽

Free Living ◽

Haematogenous Spread ◽

Primary Focus

Abstract A description is provided for Aspergillus fumigatus. Information is included on the disease caused by the organism, its transmission, geographical distribution, and hosts. HOSTS: Common as a saprophyte in soil and fermenting vegetable matter. Pathogenic to mammals (including man), birds and insects. DISEASES: The most serious diseases caused by this fungus are the acute and chronic infections of the respiratory system (aspergillosis, aspergilloma) of man (Austwick, 1965; and many other references, e.g., RMVM 3, 677; 4, 316; 4, 549, 551) and animals (Ainsworth & Austwick, 1959; Austwick, 1965). It may also infect the cardiovascular, digestive, genital, musculoskeletal, nervous, and urinary systems, such infections usually following haematogenous spread of the pathogen from a primary focus in the lungs or air sacs. It is the most common cause of mycotic abortion in cattle (Ainsworth & Austwick, 1959; Austwick, RMVM 5, 660; Dijkstra; RMVM 5, 92) and less often in horses (Hensel et al. ; RMVM 4, 1227). Aspergillus fumigatus may also infect the ear (otomycosis) and mastoid cavity, the eye and sinuses (mycoses). Aspergillosis is a major disease of birds and is a cause of considerable losses in the poultry industry, particularly of very young birds (brooder pneumonia) (Vertinskii et al. ; RMVM 5, 758; Vallejo; 5, 940). It is also common in captive wild birds, especially water birds (Ainsworth & Rewell; RMVM 1, 2090; Dathe; 4, 1948; Saez; 4, 811), but reports of infections in free-living wild birds are more rare (Beer; RMVM 4, 2177; McDiarmid; 2, 1761; Rosen, 5, 558). A. fumigatus also invades eggs. Aspergillus fumigatus spores may induce allergic reactions in man, resulting in hay fever, asthma or allergic bronchopulmonary aspergillosis. It also produces toxins (Ainsworth & Austwick, 1959; Austwick, 1965). GEOGRAPHICAL DISTRIBUTION: World-wide. TRANSMISSION: Soil and air-borne. Disease incidence appears to be related to heavy infection from house dust, mouldy hay or straw, litter, or feeding stuffs (Austwick, 1965; Austwick, RMVM 5, 3b).

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Eosinophil Deficiency Compromises Lung Defense against Aspergillus fumigatus

Infection and Immunity ◽

10.1128/iai.01172-13 ◽

2013 ◽

Vol 82 (3) ◽

pp. 1315-1325 ◽

Cited By ~ 45

Author(s):

Lauren M. Lilly ◽

Michaella Scopel ◽

Michael P. Nelson ◽

Ashley R. Burg ◽

Chad W. Dunaway ◽

...

Keyword(s):

Aspergillus Fumigatus ◽

Allergic Bronchopulmonary Aspergillosis ◽

Cell Contact ◽

Mrna Levels ◽

Colony Stimulating Factor ◽

Content Type ◽

Eosinophil Peroxidase ◽

Stimulating Factor ◽

Deficient Mice

ABSTRACTExposure to the moldAspergillus fumigatusmay result in allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, or invasive aspergillosis (IA), depending on the host's immune status. Neutrophil deficiency is the predominant risk factor for the development of IA, the most life-threatening condition associated withA. fumigatusexposure. Here we demonstrate that in addition to neutrophils, eosinophils are an important contributor to the clearance ofA. fumigatusfrom the lung. AcuteA. fumigatuschallenge in normal mice induced the recruitment of CD11b+Siglec F+Ly-6GloLy-6CnegCCR3+eosinophils to the lungs, which was accompanied by an increase in lungEpx(eosinophil peroxidase) mRNA levels. Mice deficient in the transcription factor dblGATA1, which exhibit a selective deficiency in eosinophils, demonstrated impairedA. fumigatusclearance and evidence of germinating organisms in the lung. Higher burden correlated with lower mRNA expression ofEpx(eosinophil peroxidase) andPrg2(major basic protein) as well as lower interleukin 1β (IL-1β), IL-6, IL-17A, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and CXCL1 levels. However, examination of lung inflammatory cell populations failed to demonstrate defects in monocyte/macrophage, dendritic cell, or neutrophil recruitment in dblGATA1-deficient mice, suggesting that the absence of eosinophils in dlbGATA1-deficient mice was the sole cause of impaired lung clearance. We show that eosinophils generated from bone marrow have potent killing activity againstA. fumigtausin vitro, which does not require cell contact and can be recapitulated by eosinophil whole-cell lysates. Collectively, our data support a role for eosinophils in the lung response afterA. fumigatusexposure.

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Concurrent sensitization to Aspergillus Fumigatus in tropical pulmonary eosinophilia

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2015.736 ◽

2016 ◽

Vol 81 (1-2) ◽

Author(s):

Sunil K. Chhabra ◽

Devi Jyoti Dash

Keyword(s):

Aspergillus Fumigatus ◽

Severe Asthma ◽

Lung Tissue ◽

Peripheral Blood ◽

Allergic Bronchopulmonary Aspergillosis ◽

Pulmonary Eosinophilia ◽

Blood Eosinophilia ◽

Future Risk ◽

Serum Total Ige ◽

Peripheral Blood Eosinophilia

Tropical pulmonary eosinophilia (TPE) is characterized by lung tissue and peripheral blood eosinophilia. Serum total IgE is also markedly increased in TPE. However, an association with asthma or other hypersensitivity conditions has not been described. During the diagnostic workup of three patients eventually confirmed to have TPE, hypersensitivity to the fungus, Aspergillus Fumigatus was found. However, there was no evidence of diseases of aspergillus hypersensitivity such as severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA). This association however raises the possibility of a future risk of these potentially serious allergic respiratory manifestations.RiassuntoL’eosinofilia polmonare tropicale (TPE) è caratterizzata da tessuto polmonare e eosinofilia nel sangue periferico. Anche il siero IgE totale è notevolmente aumentato in TPE. Tuttavia, un’associazione con asma o altre condizioni di ipersensibilità non è stata descritta. Durante l'iter diagnostico di tre pazienti, che alla fine si sono rivelati presentare TPE, ipersensibilità al fungo, è stato trovato l’Aspergillus fumigatus. Tuttavia, non vi era alcuna evidenza di malattie di Aspergillus ipersensibilità come l'asma grave con sensibilizzazione fungina (SAF) e aspergillosi broncopolmonare allergica (ABPA). Questa associazione pone tuttavia la possibilità di un rischio futuro di queste potenzialmente gravi manifestazioni allergiche respiratorie.

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High Prevalence of Azole-Resistant Aspergillus fumigatus in Adults with Cystic Fibrosis Exposed to Itraconazole

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05077-11 ◽

2011 ◽

Vol 56 (2) ◽

pp. 869-874 ◽

Cited By ~ 120

Author(s):

Pierre-Régis Burgel ◽

Marie-Thérèse Baixench ◽

Michaël Amsellem ◽

Etienne Audureau ◽

Jeanne Chapron ◽

...

Keyword(s):

Cystic Fibrosis ◽

Aspergillus Fumigatus ◽

Allergic Bronchopulmonary Aspergillosis ◽

Previous Treatment ◽

University Hospital ◽

Clinical Implications ◽

Content Type ◽

Microdilution Method ◽

Broth Microdilution Method ◽

High Prevalence

ABSTRACTAspergillus fumigatusis the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) orAspergillusbronchitis in CF subjects. We hypothesized thatA. fumigatusisolates in the sputum of CF subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. From June 2010 to April 2011, sputum samples from adult CF subjects at Cochin University Hospital (France) were examined systematically for the detection ofA. fumigatus. MICs ofA. fumigatusisolates against azoles were screened using Etest, and reduced susceptibility to azoles was confirmed using the CLSI broth microdilution method.A. fumigatuswas isolated from the sputum of 131/249 (52.6%) adult CF subjects, and 47/131 (35.9%) subjects had received previous treatment with itraconazole. ReducedA. fumigatussusceptibility to itraconazole (MIC, ≥2 mg/liter) was confirmed in 6/131 (4.6%) subjects. All 6 isolates also had reduced susceptibility to posaconazole (MIC, ≥0.5 mg/liter), and 3/6 isolates had reduced susceptibility to voriconazole (MIC, ≥2 mg/liter). Mutations in thecyp51Agene were detected at positions previously implicated to cause resistance in 5 isolates. Azole-resistantA. fumigatusisolates were found in 5/25 (20%) subjects exposed to itraconazole within the previous 3 years. High rates of azole-resistantA. fumigatusisolates were present in adult CF subjects and were associated with recent itraconazole exposure. Although the clinical implications of these findings will require further studies, the cautious use of itraconazole in adult CF subjects can be recommended.

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Isolation and immunochemical characterization of fractions from membranes of Aspergillus fumigatus with protease activity

Canadian Journal of Microbiology ◽

10.1139/m90-006 ◽

1990 ◽

Vol 36 (1) ◽

pp. 33-41 ◽

Cited By ~ 13

Author(s):

James E. Piechura ◽

Viswanth P. Kurup ◽

Laureen J. Daft

Keyword(s):

Aspergillus Fumigatus ◽

Protease Activity ◽

Analytical Ultracentrifugation ◽

Polyacrylamide Gel Electrophoresis ◽

Sodium Dodecyl ◽

Allergic Bronchopulmonary Aspergillosis ◽

Enzyme Linked Immunosorbent Assay ◽

Molecular Weights ◽

Crossed Immunoelectrophoresis ◽

Triton X

Two fractions exhibiting acid protease activity (AFPI and AFPII) were isolated by extraction of membrane vesicles of Aspergillus fumigatus with Triton X-100. These two fractions produced single bands in both polyacrylamide and sodium dodecyl sulfate polyacrylamide gel electrophoresis and showed apparent molecular weights of 73 000 and 43 000, respectively. Molecular weights determined by gel filtration in the absence and presence of Triton X-100 and sedimentation velocities in analytical ultracentrifugation indicated hydrophobic characteristics, since both fractions readily aggregated and complexed with Triton X-100; both exhibited elevated enzyme activities in the presence of Triton X-100. Carbohydrate content was 93% for AFPI and 85% for AFPII. The enzymatic fractions demonstrated different pH optima in the acid range as well as different temperature stabilities. Both protease fractions cross reacted in double immunodiffusion, while in crossed immunoelectrophoresis both demonstrated five precipitin peaks, each with similar patterns. AFPI demonstrated two additional precipitin peaks in crossed immunoelectrophoresis. As determined by crossed immunoaffinoelectrophoresis, the protease fractions demonstrated galactose and mannose residues. In biotin–avidin enzyme-linked immunosorbent assay both fractions reacted with allergic bronchopulmonary aspergillosis and aspergilloma sera. It can be concluded that the two fractions with protease activity of A. fumigatus reported here may be of significance in Aspergillus-induced diseases. Key words: Aspergillus, membrane, allergens, proteases, aspergillosis.

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