Multifunctional antigens of A-fumigatus and specific antibodies

The majority of Aspergillus-induced infections in man are caused by the pat hogenic fungus A. fumigatus, which secretes biologically and immunologicall y active glycosylated and nonglycosylated proteins. The complexity in the a ntigenic structure of A. fumigatus and the varying host immune responses le ad to a wide spectrum of clinical conditions such as allergic bronchopulmon ary aspergillosis (ABPA), aspergilloma, and invasive aspergillosis. It is r eported 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 react ions are involved in pathogenesis. High levels of specific IgE and IgG anti bodies in these patients are of diagnostic value. Molecular characterizatio n 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 nonbind ing allergen/antigen (18 kDa, Asp fI) have a multifunctional nature. The mu ltifunctional nature of these antigens may play an important role in the pa thogenesis of the disease. Significant amounts of a major allergen/antigen of molecular weight 18 kDa is excreted in large amounts through the urine o f patients with invasive aspergillosis. Studies on the structure-function r elationship of the 18-kDa allergen/antigen revealed the involvement of tryp tophan residues in binding with monoclonal antibodies (MAbs). Also, the his tidine residues and cysteine disulfide bonds of the 18-kDa allergen are inv olved 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 p atients have necessitated studies on the functional properties of the antib odies. The present study shows significant immunoreactivity of antibodies i n patients of ABPA to fibronectin and collagen. Analysis of IgG antibodies from the patients of ABPA showed the presence of DNA-cleaving activity. The se observations offer a new line of thinking in understanding the mechanism of pathogenesis of Aspergillus-induced clinical manifestations, and may le ad to novel approaches to intervention in the inflammation and infection ca used by fungal pathogens.