Viswanath P. Kurup, Ph.D.1 and Reto Crameri, Ph.D.2
1Professor of Pediatrics and Medicine, Medical College of Wisconsin and Veterans Affairs Research Service, Milwaukee, Wisconsin USA, 2Professor of Molecular Genetics, Swiss Institute of Allergy & Asthma Research, Davos, Switzerland
Address Correspondence to:
Viswanath P. Kurup, Ph.D.
V A Medical Center
Research Service 151-I
5000 West National Avenue
Milwaukee, WI 53295
USA
Phone No: 414-384-2000 X41459/41510, Fax No: 414-382-5374,
E-mail: vkurup@mcw.edu
Allergic bronchopulmonary aspergillosis (ABPA) is described as an
immunological disease with immediate and late cutaneous reactivity
to Aspergillus antigens (Kurup and Apter, 1998b; Kurup
et al., 1999; Patterson et al., 1982). This disease,
along with other allergic diseases such as allergic asthma,
rhinitis, and non-allergic diseases such as pulmonary
aspergillosis, systemic aspergillosis, and Aspergillus
fungus balls (aspergilloma), are caused by the saprophytic mold
Aspergillus fumigatus (Kurup and Banerjee,
1997). Aspergillus fumigatus is the most frequently
encountered pathogen/allergen among the more than 100 known
species of Aspergillus. Among the non-allergic diseases
caused by Aspergillus, pulmonary and systemic aspergillosis
are the most common and has a very high mortality and morbidity
rate (Bardana, 1980). This disease is usually seen in individuals
with altered immune response such as patients undergoing
immunosuppressive, broad spectrum antibiotic or high dose
corticosteroid therapy or those with underlying diseases such as
AIDS, cancer, and chronic diseases (Cenci et al., 2000;
Denning, 1998; Denning et al., 1991).
ABPA is seen in patients with atopy and asthma and invariably all patients show very high levels of total and A. fumigatus specific IgE in the sera (Greenberger, 1988; Patterson et al., 1977; Rosenberg et al., 1977b; Varkey, 1998). Precipitating antibodies against the antigens can also be detected in the sera and represent one of the criteria for the diagnosis of the disease (Greenberger, 1988). Central bronchiectasis with normal distal tapering and elevated number of eosinophils in peripheral blood and lung are significant features ABPA (Rosenberg, et al., 1977a). However, all these clinical features suggested for the diagnosis of ABPA may not be present at all times (Kurup et al., 2000). Depending on the stage of the disease, treatment with steroids and/or controlling the underlying conditions may help to improve the health of the patients.
For reliable early diagnosis of ABPA more dependable in vitro parameters need to be employed to supplement the clinical features (Varkey, 1998). As the serum antibodies in ABPA patients showed marked elevation in IgG and IgE-specific antibodies against fungal extract, this characteristic have been used widely in the laboratory diagnosis of ABPA. The level of A. fumigatus specific antibodies in the sera allows differentiation of patients with asthma and Aspergillus sensitization from those suffering from ABPA alone. Precipitating antibodies can be demonstrable in up to 90% or more of patients with ABPA.
Exposure to A. fumigatus through either inhalation of spores or fungal colonization in the bronchi results in asthmatic reaction. The eosinophilic infiltration and mast cell degranulation in response to A. fumigatus allergens and IgE interaction results in the release of additional proinflammatory mediators that play a major role in the pathogenesis of ABPA. The mast cell and eosinophil degranulation induce further chemotaxis of inflammatory cells including CD4+ lymphocytes and eosinophils (Kurup and Kumar, 1991).
Immunodiagnosis of ABPA is significantly affected by the lack of reliable antigen preparations. The fungi belonging to the genus Aspergillus produce a wide range of antigenic/allergenic components. Some are metabolic products secreted outside, some are surface bound, while others are cytoplasmic and released only by autolysis. The complex nature of the antigens also results from the uniqueness of conidial and hyphal antigens. The inherent variability detected among strains further aggravated identification and purification of antigen involved in the pathogenesis of the disease (Sarma et al., 1998). The major problems in the diagnosis, until recently, have been the lack of purified and standardized Aspergillus antigens and the lack of knowledge on molecular and structural features of these allergens. However, of late, some of these problems received due attention and today we have a number of useful purified recombinant antigens from A. fumigatus for reliable immunological studies of the disease and for improvement of the diagnosis (Banerjee and Kurup, 1998). The present article focuses on the recent progress made in the field of allergen cloning, characterization, and standardized production.
Aspergillus
Allergens:
Cloning Allergens from A. fumigatus:
Recombinant Allergens from A. fumigatus:
Table
1:
Table 2:
Future Direction:
Acknowledgements
REFERENCES