Multifunctional antigens of A. fumigatus and specific antibodies

The majority of Aspergillus-induced infections in man are caused by the pathogenic fungus A. fumigatus, which secretes biologically and immunologically active glycosylated and nonglycosylated proteins. The complexity in the antigenic structure of A. fumigatus and the varying host immune responses lead to a wide spectrum of clinical conditions such as allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, and invasive aspergillosis. It is reported that 15-20% of allergic asthmatics suffer from Aspergillus-induced allergies. The incidence of opportunistic infections, including Aspergillus infections, has risen because of the increase in the incidence of HIV and tuberculosis. Allergic bronchopulmonary aspergillosis is an immunologically significant clinical form where type I and type III hypersensitivity reactions are involved in pathogenesis. High levels of specific IgE and IgG antibodies in these patients are of diagnostic value. Molecular characterization of certain immunodominant allergens and antigens of A. fumigatus revealed the presence of complex carbohydrate moieties, heat-shock proteins, enzyme activities such as elastase, protease, catalase, dismutase, and cytotoxic ribonuclease. A Con A binding allergen/antigen (45 kDa) and Con A nonbinding allergen/antigen (18 kDa, Asp fI) have a multifunctional nature. The multifunctional nature of these antigens may play an important role in the pathogenesis of the disease. Significant amounts of a major allergen/antigen of molecular weight 18 kDa is excreted in large amounts through the urine of patients with invasive aspergillosis. Studies on the structure-function relationship of the 18-kDa allergen/antigen revealed the involvement of tryptophan residues in binding with monoclonal antibodies (MAbs). Also, the histidine residues and cysteine disulfide bonds of the 18-kDa allergen are involved in its catalytic activity. The high load of multifunctional antigens in the serum of patients for prolonged periods, the presence of high levels of specific antibodies, and the absence of protective antibodies in ABPA patients have necessitated studies on the functional properties of the antibodies. The present study shows significant immunoreactivity of antibodies in patients of ABPA to fibronectin and collagen. Analysis of IgG antibodies from the patients of ABPA showed the presence of DNA-cleaving activity. These observations offer a new line of thinking in understanding the mechanism of pathogenesis of Aspergillus-induced clinical manifestations, and may lead to novel approaches to intervention in the inflammation and infection caused by fungal pathogens.