Skin test reactivity to 2 recombinant Aspergillus fumigatus allergens in Afumigatus-sensitized asthmatic subjects allows diagnostic separation of allergic bronchopulmonary aspergillosis from fungal sensitization

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 syndrom e that is difficult to diagnose. A clear distinction between allergic sensi tization to A fumigatus and ABPA is essential for therapy to prevent deteri oration of pulmonary function in subjects with ABPA, Objective: This study was carried out to determine the specificity and sens itivity of 2 A fumigatus allergens for the in vivo diagnosis of ABPA, Methods: Serologic investigations with recombinant A fumigatus allergens in dicated the existence of disease-specific allergens that are useful for dis crimination between ABPA and fungal sensitization. However, serologic studi es 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 pro tein with unknown biologic function, and rAsp f 6 (manganese superoxide dis mutase) are able to provoke immediate skin reactions exclusively in patient s with ABPA. The reactions, which are elicited by a few nonograms of the al lergens, strictly depend on the presence of allergen-specific serum IgE. Th e IgE cut-off values for positive skin reactions to rAsp f 4 and rAsp f 6 o f 0.9 and 1.2 kU(A)/L correspond to allergen-specific serum concentrations of 2 to 3 mu g/L and allow a sensitive, highly specific diagnosis of ABPA. Conclusions: In contrast to fungal extracts, rAsp f 4 and rAsp f 6 allow di scrimination between ABPA and sensitization to A fumigatus. Moreover, the a llergens are suitable for an automated serologic diagnosis of ABPA, facilit ating their introduction in clinical practice.