Increased antigen-specific Th-2 response in allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis

The majority of patients with cystic fibrosis (CF) become colonized with As pergillus fumigatus (A. fumigatus) in the lower respiratory tract, the prev alence being up to 60%, Between 1-11% of CF patients develop allergic bronc hopulmonary aspergillosis (ABPA). Previous studies of ABPA in selected pati ents suffering from cystic fibrosis or atopic asthma have suggested a patho genic role for antigen-specific "Th2-like" T lymphocytes. The aim of this s tudy was to evaluate the quantitative importance of such Th2 cells, using i mproved techniques for measuring interleukin-4 (IL-4) and IL-5 secretion in unseparated peripheral blood mononuclear cell (PBMC) suspensions from CF p atients with ABPA and from a control group without ABPA. Thus, 20 patients with CF, heavily colonized with A. fumigatus in the lower respiratory tract , were studied: 10 patients with ABPA, and 10 without. Unseparated PBMC wer e stimulated in vitro by A. fumigatus antigen and by an unrelated antigen ( tetanus toroid) as a control. After 6 days of stimulation, IL-4 and IL-5 (m arkers for Th2 cell activity) and interferon-gamma (IFN-gamma) (marker for Th1 cell activity) were quantified in the supernatants by enzyme-linked imm unosorbent assay. PBMC from ABPA patients secreted significantly higher amounts of IL-4, i.e. , 0.48 (0.15-0.8) ng/mL (median (range)), and IL-5, 37.64 (0.32-82.85) ng/m L, compared to secretions obtained in non-ABPA CF controls of 0.07 (0.04-0. 16) ng/mL and 3.00 (0.10-5.09) ng/mL, respectively (P < 0.01 for both). IFN -gamma secretion was similar in the two groups, amounting to 21.5 (2.05-72. 5) ng/mL in ABPA patients vs. 20.75 (1.80-54.0) ng/mL in non-ABPA patients (P = 0.47). No significant differences were obtained in the cytokine secret ion induced by tetanus toroid stimulation between the two groups. We conclude that ABPA in CF patients is associated with an antigen-specific , The-like T-cell immune response, as indicated by excessive secretion of I L-4 and IL-5. Pediatr Pulmonol, 1999; 27:74-79, (C) 1999 Wiley-Liss, Inc.