© 2007 American Thoracic Society
Specific IgE against Recombinant Allergens in Allergic Bronchopulmonary AspergillosisFrom the Authors:We appreciate the comments on our recent article (1), and fully agree with the letter authors that the diagnosis of allergic bronchopulmonary aspergillosis (ABPA), especially in patients suffering from cystic fibrosis (CF), remains a challenge. The classical diagnosis of ABPA in CF (2) is based on a combination of clinical (wheezing, pulmonary infiltrates, positive skin test to Aspergillus fumigatus extracts), and laboratory criteria (A. fumigatus in sputum, elevated total serum IgE levels, elevated A. fumigatus–specific IgG and IgE antibodies in serum). Six of the seven criteria have to be present for a reliable diagnosis. Unfortunately, the presence of central bronchiectasis, the most reliable criterion for the diagnosis of ABPA in patients with asthma, is not applicable to CF, since a high incidence of central bronchiectasis in the absence of A. fumigatus sensitization is found with this disorder (3). We have developed an array of recombinant A. fumigatus allergens and tested their diagnostic value in A. fumigatus–sensitized patients suffering from allergic asthma or CF. The aim of these studies was to confirm ABPA suspected from clinical signs and not to provide an alternative diagnosis method. The rationale behind a discriminatory property of some recombinant allergens like MnSOD (Asp f 6) is that they are expressed only during the late phase of A. fumigatus germination (4) and are therefore unlikely to be seen by the immune system of A. fumigatus–sensitized individuals without ABPA. In contrast, secreted allergens like Asp f 1 are seen by the immune system of all exposed individuals and therefore potentially able to induce an IgE immune response in all atopic individuals (5). Because the fungus is able to produce more that 80 allergens (6), it cannot be expected that all A. fumigatus–sensitized patients mount an IgE response against all allergens, limiting the sensitivity of a diagnosis based on single molecules. A further complication related to the serology of ABPA is that the A. fumigatus–specific IgG and IgE levels vary depending on the stage of the disease. Therefore, patients with ABPA should be stratified according to the phase of the disease for a correct diagnosis (7). If this stratification is taken into account, the diagnosis of ABPA based on recombinant allergens is quite reliable and highly specific, but the sensitivity never reaches 100%. From the 65 patients with asthma analyzed by Giavina-Bianchi, only 26 are RAST positive to A. fumigatus and, therefore, at potential risk to develop ABPA. The majority of the patients, 39 subjects, do not show any A. fumigatus–specific IgE RAST and are consistently negative if tested for IgE against the recombinant allergens. They would not be considered as A. fumigatus–sensitized in normal allergy screening. Among the 26 RAST-positive patients, 19 (70%) developed an IgE response against recombinant allergens, a figure similar to other studies performed with recombinant A. fumigatus allergens. We do not know the reason for the discrepancy between the skin prick test and A. fumigatus–specific RAST observed by Giavina-Bianchi. However, as pointed out by Greenberger (3), in patients with asthma only proximal bronchiectasis (in the absence of distal bronchiectasis) and elevated A. fumigatus–specific serum IgE and IgG are specific criteria for the diagnosis of ABPA. Therefore, elevated serum IgE and a positive skin test to the fungus should be demonstrated before considering ABPA as a possible reason for pulmonary complications in patients with asthma or CF.
Swiss Institute of Allergy and Asthma Research (SIAF) Davos, Switzerland
University of Berne, Berne, Switzerland FOOTNOTES Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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