Lymphocytes in allergic bronchopulmonary aspergillosis.
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease mediated by an allergic late-phase inflammatory response to Aspergillus fumigatus antigens. ABPA is characterized by markedly elevated Aspergillus-specific and total IgE levels and eosinophilia, and manifested by wheezing, pulmonary infiltrates and bronchiectasis and fibrosis, which affect asthmatic and cystic fibrosis (CF) patients. In the pathogenesis of ABPA, A. fumigatus proteases play a role in facilitation of antigen transport across the epithelial cell layer by damaging the epithelial integrity and by a direct interaction with epithelial cell surface receptors, resulting in pro-inflammatory cytokine production and corresponding inflammatory responses. In genetically susceptible asthmatic and CF patients, this leads to an allergic inflammatory response to Aspergillus allergens. A genetic susceptibility is HLA-DR restriction demonstrated by increased frequency of HLA-DR2 and/or DR5 and lack HLA-DQ2. IL-4 plays a central role in the development of allergic inflammatory responses. Our group has demonstrated that ABPA patients have increased sensitivity to IL-4 stimulation and skewing of Th2 responses to Aspergillus allergens in ABPA subjects and a Th1 response in non-ABPA subjects. Interestingly, Aspergillus allergens stimulate IL-10 synthesis is both ABPA and non-ABPA subjects.
Knutsen
Alan P
AP
Division of Allergy, Saint Louis University Health Sciences Center, 3662 Park Avenue, St. Louis, MO 63110, USA. knutsenm@slu.edu
D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000473:pathology*; D006801:Humans; D008214:Lymphocytes / Q000502:physiology*