IgE down regulation and cytokine induction by Aspergillus antigens in human allergic bronchopulmonary aspergillosis.
Allergic bronchopulmonary aspergillosis (ABPA), occurring primarily in patients with asthma or cystic fibrosis (CF), is a hypersensitivity reaction to Aspergillus fumigatus (Af), and is characterized by increased serum IgE levels and peripheral blood and pulmonary eosinophilia. We evaluated the IgE and cytokine profile in ABPA through enzyme-linked immunosorbent assay (ELISA), and evaluated eosinophil activity with the eosinophil peroxidase (EPO) assay. IgE and cytokines were measured in supernatants from cultures of peripheral blood mononuclear cells (PBMC) from three subject groups: ABPA patients, patients with asthma, and healthy individuals. All cultures for the three subject groups were studied in the presence and absence of two purified Af antigens (the 35-kD antigen and heat shock protein 1). We found that increased in vitro levels of IgE in unstimulated PBMC culture supernatants correlated significantly with serum IgE concentrations in ABPA patients. We measured a decrease in IgE levels of up to 75% of baseline values in supernatants from PBMC cultured with Af antigens. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) concentrations in cultures with Af were increased in ABPA, whereas concentrations of IL-4 did not differ in the three subject groups. An inverse relation was noted between the changes in IgE and IFN-gamma measured in 4 of 5 ABPA patients. The PBMC supernatants also promoted EPO activity in purified eosinophils from ABPA patients, and to a lesser extent in purified eosinophils from healthy subjects. These results show that the 35-kD antigen and HSP1 from Af downregulate IgE in vitro but are capable of inducing eosinophilia in ABPA. Further studies could result in the characterization of epitopes leading to these disparate effects. An identification of the IgE-down-regulating epitopes in Af antigens might have therapeutic significance.
Murali
P S
PS
Department of Medicine, Medical College of Wisconsin, VA Medical Center, Milwaukee 53295-1000, USA.
Kurup
V P
VP
Bansal
N K
NK
Fink
J N
JN
Greenberger
P A
PA
D000328:Adult; D000368:Aged; D000946:Antigens, Fungal / Q000494:pharmacology*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000276:immunology*; D001249:Asthma / Q000150:complications; D018929:Cell Culture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010544:Peroxidases / Q000378:metabolism
D000946:Antigens, Fungal; D016207:Cytokines; D007073:Immunoglobulin E; D047209:Eosinophil Peroxidase; D010544:Peroxidases