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

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. This study was carried out to determine the specificity and sensitivity of 2 A fumigatus allergens for the in vivo diagnosis of ABPA. 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. 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. 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.