An overview of allergic bronchopulmonary aspergillosis with some new insights.

Allergic bronchopulmonary aspergillosis (ABPA) occurs as a complication of bronchial asthma or cystic fibrosis (CF). The diagnostic criteria speak to an exaggerated type I hypersensitivity response to the ubiquitous organism Aspergillus fumigatus. Immunologic parameters indicative of Aspergillus sensitization in CF may be lost spontaneously. Therefore, it is important that the diagnosis of ABPA in CF include clinical parameters. CF transmembrane regulator gene mutations may occur in asthmatic ABPA patients indicating a subset of ABPA patients that warrant further study to exclude the diagnosis of CF. The extensive tissue damage seen in ABPA may, in part, be caused by proteases released from aspergillus. Host characteristics may predispose to the development of ABPA. It appears that human leukocyte antigen DR2 and particularly DRB1*1503 and *1501 alleles represent significant ABPA susceptibility genes with the possibility that human leukocyte antigen DQ2 allele confers protection in the non-ABPA population. These findings may offer an additional clinical aid in early diagnosis and provide insight into T-cell reactivity in ABPA that may lead to the development of specific immunotherapy.

MHC restriction in allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a rare complication in patients with asthma but more common in patients with cystic fibrosis. In the presence of the fungus Aspergillus fumigatus (Af) in the lower respiratory tract, patients mount a heightened IgG and IgE humoral response specific for Af antigens. Studies on ABPA have suggested a pathogenic role for antigen specific CD4+ Th2 like T lymphocytes producing increased levels of IL-4 and IL-5. MHC class II genes coding for highly polymorphic HLA molecules have been shown to be the likely candidates for controlling immune responses to common allergens. However there has been a lack of information on the pathophysiological role of HLA genes in the development of ABPA. This review describes an association between HLA- class II alleles and the specific responses to Af antigen (Asp f 1) in ABPA. These studies focused on MHC restriction and distribution of HLA- class II alleles in two groups of unrelated North American Caucasian patients with cystic fibrosis and/or asthma. One group consisted of patients with a confirmed diagnosis of ABPA and a second group of patients with Af sensitivity but no ABPA. HLA association studies revealed that the predisposition to develop ABPA is associated with HLA-DR2 and DR5, and possibly DR4 or DR7. A strong association of HLA-DR antigens with ABPA reflects that HLA-DR molecules may present disease-causing peptides. On the other hand a significant association of HLA-DQ2 with Af sensitive nonABPA indicates the involvement of HLA-DQ molecules in protection. A combination of these genetic factors determines the outcome of ABPA in patients with cystic fibrosis and asthma.

T-cell receptor bias in patients with allergic bronchopulmonary aspergillosis.

CD4(+) Th2 helper cell mediated immune responses have been shown to play a crucial role in the pathogenesis of ABPA. HLA and TCR are the candidate genes, which can influence the specificity of these responses. We have previously established a strong association of HLA DR2/5 in ABPA susceptibility. The study was designed to determine whether allergen specific T cell express a limited usage of T cell receptor (TCR) Vbeta gene repertoire in ABPA and to find an association of susceptible HLA-DR determinants with the identified TCR gene segments. TCR Vbeta typing was performed on antigen specific T cell lines from 14 ABPA and 12 nonABPA patients. The majority of ABPA patients (86%) expressed allergen specific T cells with Vbeta13 genes indicating its role in susceptibility, whereas in nonABPA controls, Vbeta1 genes T cell repertoires were predominantly expressed. The unrestricted pattern of Vbeta gene amplification seen before antigen stimulation suggests an oligoclonal expansion of a specific T cell population in response to the allergen Asp f 1 in ABPA and nonABPA patients. The increased usage of Vbeta13 in ABPA and Vbeta1 in nonABPA indicates their importance in susceptibility and resistance, respectively.