T- and B-cell dysregulation of IgE synthesis in cystic fibrosis patients with allergic bronchopulmonary aspergillosis

Abstract

Since Aspergillus fumigatus (Af)-specific and polyclonal serum IgE levels are characteristically elevated in patients with allergic bronchopulmonary aspergillosis (ABPA), we evaluated in vitro regulation of IgE synthesis in cystic fibrosis (CF) patients with ABPA. We studied 11 CF patients with ABPA, 37 patients with positive Af prick skin tests and/or IgG precipitating antibodies ( ST PPT+ ), and 35 patients with no humoral or skin responses to Aspergillus ( ST PPT− ). Mean serum IgE concentration was significantly elevated in CF subjects with ABPA compared to ST PPT+ and ST PPT− patients, 2866 vs 303 and 61 IU/ml, respectively ( P < 0.01). In vitro studies demonstrated that ABPA patients' B cells spontaneously synthesized significantly increased amounts of IgE compared to ST PPT positive and negative subjects, 1980 vs 220 and 13 pg/ml, respectively ( P < 0.01). In addition, preformed B-cell-associated IgE was also significantly elevated in ABPA subjects ( P < 0.01), indicating prior in vivo activation. Supernatant cultures of Af-stimulated T cells from ABPA subjects significantly induced allogeneic B-cell IgE synthesis compared to ST PPT positive and negative CF subjects, 206 vs 13 and 4 pg/ml, respectively ( P < 0.01). Thus T cells stimulated with Aspergillus antigens secrete cytokines that induce B-cell IgE synthesis in ABPA subjects. B-cell IgE hyperactivity is manifested by in vivo and in vitro increased IgE concentrations. Analyses of T-cell regulation and B-cell IgE synthesis distinguish CF subjects with ABPA from Aspergillus sensitive non-ABPA subjects.