Basophil and lymphocyte functional assays with Aspergillus molecules:
the case for ABPA
Abstract
Background. Allergic bronchopulmonary aspergillosis (ABPA) is an
underestimated allergic disease due to Aspergillus fumigatus (AF). The
main diagnostic criteria for ABPA rely on the evaluation of
immunoglobulin (Ig) E and IgG responses to AF extracts, although these
cannot discriminate AF-sensitization from ABPA. Objectives. To evaluate
the performance of cellular functional assays with extract and molecular
AF allergens in ABPA. Methods. A prospective cohort of 67 patients (6
ABPA) was investigated with basophil activation test (BAT) and
lymphocyte stimulation test (LST) with AF extract. Nine patients were
further investigated for BAT responses to molecular AF components: Asp f
1, Asp f 2, Asp f 3, Asp f 4 and Asp f 6. BAT supernatant was assessed
for cytokine production. Results. BAT with AF extract with an optimized
cutoff displayed 100% sensitivity and 77.6 % specificity for ABPA
diagnosis. Among patients with positive BAT to AF, BAT with Asp f 4 was
significantly higher in ABPA patients at 10 ng/mL (mean basophil
stimulation index 10.56 in ABPA vs 1.24 in non-ABPA patients, p =
0.0002). High LST with AF extract was associated with ABPA occurrence
three months after the test. No significant ex vivo cytokine release was
observed in BAT supernatants. Conclusion. BAT with AF is a promising
diagnostic biomarker in the context of suspected ABPA, which can be
further improved with AF molecular allergens, especially Asp f 4. LST
with detection of AF-induced activation of peripheral T cells suggests
an underlying pathophysiological process and may predict ABPA
occurrence.