The major objectives of this proposal are to study the epidemiology of allergic bronchopulmonary aspergillosis (ABA) in patients with cystic fibrosis (CF) and to investigate the contribution and participation of a number of immunologic responses in the pathogenesis of ABA. The incidence of ABA in CF appears unusually high. We will determine the true incidence of ABA in our CF population and will moniter various parameters in order to predict the development of ABA in CF patients. These parameters include clinical evaluation for increased bronchospasm, sputum production, low grade temperature, and pulmonary infiltrates. Immunologic parameters to be measured include immediate skin reactivity to aspergillus fumigatus (AF) serum precipitins to AF, total serum IgE, IgE and IgG specific for AF, peripheral blood eosinophilia, and in vitro lymphocyte response to AF. Patients with known ABA with and without CF will be studied utilizing a variety of immunologic tests in order to better delineate the true pathogenesis of ABA. Cell mediated immunity to AF will be determined by intradermal skin testing following pharmacologic ablation of the immediate skin test reaction, and by in vitro response of peripheral blood lymphocytes to AF. The abnormally high IgE levels seen in ABA might be due to either excessive T helper cell activity or decreased T suppressor cell activity. T helper and T suppressor cells in ABA patients will be quantitated by means of a fluorescence activated cell sorter. Biologic or functional activity of the two T cell subsets will be determined by co-culturing T cells of ABA patients with control B cells and observing the effect on in vitro IgE production by normal B cells, and also by co-culturing ABA cells with a human IgE secreting myeloma cell line.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL030652-02
Application #
3341670
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Saint Louis University
Department
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
Slavin, R G; Gleich, G J; Hutcheson, P S et al. (1992) Localization of IgE to lung germinal lymphoid follicles in a patient with allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 90:1006-8
Knutsen, A; Slavin, R G (1992) Allergic bronchopulmonary mycosis complicating cystic fibrosis. Semin Respir Infect 7:179-92
Hutcheson, P S; Rejent, A J; Slavin, R G (1991) Variability in parameters of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. J Allergy Clin Immunol 88:390-4
Knutsen, A P; Mueller, K R (1990) T cell cytotoxicity in cystic fibrosis: relationship to pulmonary status. Int Arch Allergy Appl Immunol 93:54-8
Slavin, R G; Bedrossian, C W; Hutcheson, P S et al. (1988) A pathologic study of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 81:718-25
Slavin, R G; Hutcheson, P S; Knutsen, A P (1987) Participation of cell-mediated immunity in allergic bronchopulmonary aspergillosis. Int Arch Allergy Appl Immunol 83:337-40