TY - JOUR
T1 - IgE down regulation and cytokine induction by Aspergillus antigens in human allergic bronchopulmonary aspergillosis
AU - Murali, Pazhayannur S.
AU - Kurup, Viswanath P.
AU - Bansal, Naveen K.
AU - Fink, Jordan N.
AU - Greenberger, Paul A.
N1 - Funding Information:
From the Department of Medicine, Medical College of Wisconsin; Research Service, VA Medical Center, Milwaukee; Department of Mathematics, Statistics and Computer Science, Marquette University; and Division of Allergy-Immunology, Northwestern University Medical School. Supported by the American Lung Association of Wisconsin and the US Veterans Affairs Medical Research Service. Dr, Paul A. Greenberger was supported by the Ernest S, Bazley grant to Northwestern Memorial Hospital and Northwestern University.
PY - 1998/3
Y1 - 1998/3
N2 - 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 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-γ 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.
AB - 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 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-γ 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.
UR - http://www.scopus.com/inward/record.url?scp=0032033424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032033424&partnerID=8YFLogxK
U2 - 10.1016/S0022-2143(98)90094-4
DO - 10.1016/S0022-2143(98)90094-4
M3 - Article
C2 - 9523846
AN - SCOPUS:0032033424
VL - 131
SP - 228
EP - 235
JO - Translational Research
JF - Translational Research
SN - 1931-5244
IS - 3
ER -