Purpose:The opportunistic fungus A. fumigatus (Af) colonizes the airways of 25-50% of cystic fibrosis (CF) patients, with some further progressing towards allergic bronchopulmonary aspergillosis (ABPA). ABPA significantly impacts short- and long-term prognoses in CF, yet may be avoided by early diagnosis and treatment. However, the diagnosis of CF-ABPA is clinically challenging, due in large part to the absence of an objective biological test. Since blood basophils play a major role in allergic responses, we hypothesized that discrete changes on their surface activation pattern could discriminate CF patients with ABPA from those without.
Method: We used a direct flow cytometry assay to measure surface CD203c and CD63 levels on blood basophils, at baseline and upon rapid in vitro activation with Af allergen, in 5 groups of subjects: (A) CF patients with Af colonization but without ABPA (N=11); (B) CF-ABPA patients (N=8); (C) CF-ABPA patients whose treatment includes anti-immunoglobulin E (omalizumab) (N=2); (D) CF patients without Af colonization and without ABPA (N=5) and (E) healthy controls (N=11). The quantity of histamine in the plasma was measured by mass spectrometry.
Results: In the CF-ABPA group, basophil CD203c levels and histamine levels increased significantly upon Af allergen stimulation (CD203c levels: P<10-3, compared to the three other groups of patients). This increase was Af allergen-specific, since stimulation with a non-offending allergen did not increase surface CD203c or plasma histamine from subjects in any of the groups (CD203c levels : P<10-2 ). Basophil CD203c levels upon Af allergen stimulation provided very good predictive value for discriminating CF-ABPA from CF patients with Af colonization but without ABPA (area under the receiver operating characteristics curve = 0.92, P<10-3). In our preliminary results, basophil CD203c levels increased also upon recombinant A. fumigatus allergen 1 (Asp f 1) stimulation.
Conclusion: These results support the notion that basophils play a role in the pathogenesis of CF-ABPA and can be used to diagnose and monitor this condition clinically with a simple and minimally invasive blood assay.
Full conference title:
- AAA 5th (2012)