title: Skin test reactivity to 2 recombinant Aspergillus fumigatus allergens in A fumigatus-sensitized asthmatic subjects allows diagnostic separation of allergic bronchopulmonary aspergillosis from fungal sensitization.
abstract: BACKGROUND
  Aspergillus fumigatus, an opportunistic pathogen, is associated with an impressive list of pulmonary complications. Among these, allergic bronchopulmonary aspergillosis (ABPA) represents a complex clinical syndrome that is difficult to diagnose. A clear distinction between allergic sensitization to A fumigatus and ABPA is essential for therapy to prevent deterioration of pulmonary function in subjects with ABPA.
  
  
  OBJECTIVE
  This study was carried out to determine the specificity and sensitivity of 2 A fumigatus allergens for the in vivo diagnosis of ABPA.
  
  
  METHODS
  Serologic investigations with recombinant A fumigatus allergens indicated the existence of disease-specific allergens that are useful for discrimination between ABPA and fungal sensitization. However, serologic studies fail to indicate the allergen-specific IgE levels required to elicit an allergic reaction in vivo.
  
  
  RESULTS
  We show that the recombinant A fumigatus allergens rAsp f 4, a protein with unknown biologic function, and rAsp f 6 (manganese superoxide dismutase) are able to provoke immediate skin reactions exclusively in patients with ABPA. The reactions, which are elicited by a few nonograms of the allergens, strictly depend on the presence of allergen-specific serum IgE. The IgE cut-off values for positive skin reactions to rAsp f 4 and rAsp f 6 of 0.9 and 1.2 kU(A)/L correspond to allergen-specific serum concentrations of 2 to 3 microg/L and allow a sensitive, highly specific diagnosis of ABPA.
  
  
  CONCLUSIONS
  In contrast to fungal extracts, rAsp f 4 and rAsp f 6 allow discrimination between ABPA and sensitization to A fumigatus. Moreover, the allergens are suitable for an automated serologic diagnosis of ABPA, facilitating their introduction in clinical practice.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Hemmann
authors.forename: G
authors.initials: G
authors.lastname: Menz
authors.forename: C
authors.initials: C
authors.lastname: Ismail
authors.forename: K
authors.initials: K
authors.lastname: Blaser
authors.forename: R
authors.initials: R
authors.lastname: Crameri
mesh_terms: D000328:Adult; D000368:Aged; D000485:Allergens / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D052179:Antigens, Plant; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology*; D001249:Asthma / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D003937:Diagnosis, Differential; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007428:Intradermal Tests; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D013482:Superoxide Dismutase / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000485:Allergens; D052179:Antigens, Plant; C115316:Asp f 4 allergen; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E; C115317:Asp f 6 allergen; D013482:Superoxide Dismutase