Recombinant allergens combined with biological markers in the diagnosis of allergic bronchopulmonary aspergillosis in cystic fibrosis patients

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a frequent complication in cystic fibrosis patients. The diagnosis remains difficult and requires a combination of clinical, radiological, biological, and mycological criteria. The aim of this study was to analyze the added value of two recombinant antigens, rAspf4 and rAspf6, associated with the detection of specific IgG; precipitins; total IgE; and Aspergillus fumigatus in sputum for the diagnosis of ABPA. In a retrospective study, we determined the specific IgE responses to these recombinants in 133 sera of 65 cystic fibrosis patients. We selected an average of five serum samples from each of the 17 patients with ABPA (13 proven and 4 probable ABPA) and from 3 patients with Aspergillus bronchitis and rhinosinusitis. One serum sample for the 45 patients without ABPA was tested. The sensitivity of specific IgE detection against rAspf4 calculated per patient (92.3%) was significantly higher (P < 0.05) than that of rAspf6 (53.8%). When rAspf4 IgE detection was associated with anti-Aspergillus IgG enzyme-linked immunosorbent assay (ELISA) and precipitin detection, the sensitivity rose to 100%. The specificities of rAspf4 and rAspf6 IgE detection were 93.7% and 91.6%, respectively. Other diagnostic criteria had slightly lower specificities (87.5% for anti-Aspergillus IgG ELISA, 89.6% for precipitins, 84.4% for total IgE, and 85.0% for positive A. fumigatus culture in sputum). In conclusion, this retrospective study showed the relevance of rAspf4 IgE detection, in combination with other biological markers (Aspergillus IgG ELISA, precipitins, and total IgE), for improving the biological diagnosis of ABPA.

FIG. 1.

Mean results obtained for three groups of cystic fibrosis patients, 13 with ABPA, 3 with other fungal diseases, and 45 without ABPA. The mean values of IgE detection using rAspf4 and rAspf6, as well as specific IgG ELISA detection, were multiplied by 10; total IgE detection was multiplied by 10⁻² in order to obtain the same range values. The results of the samples collected before diagnosis of proven ABPA were excluded. Significant differences between the ABPA patient group and the control group (patients without ABPA) were observed. **, P < 0.001 for rAspf4, specific IgG, and total IgE; *, P < 0.05 for rAspf6. No significant difference was observed for the detection of Aspergillus in the sputum. Statistical analysis was not performed for the group of three patients with bronchitis or sinusitis, as it was too small.