The effects of age on isotypic antibody responses to Aspergillus fumigatus: Implications regarding in vitro measurements

The demonstration of elevated serum immunoglobulin E (IgE), immunoglobulin G (IgG), and immunoglobulin A (IgA) antibodies to Aspergillus fumigatus (Af) is a valuable aid in the serodiagnosis of allergic bronchopulmonary aspergillosis (ABPA). It is important to recognize cases of ABPA, because repeated untreated episodes of pulmonary infiltrates can result in bronchiectasis and even fatal fibrotic lung disease. Serum samples from patients with ABPA have increased isotypic antibodies to Af when compared with patients with asthma and immediate cutaneous reactivity but in whom ABPA has been excluded. There is little information regarding age-related changes of isotypic antibodies to a specific allergen or in comparison of such changes with age-related changes in total class-specific antibody. We determined IgE-Af, IgG-Af, and IgA-Af and total IgE, IgG, and IgA concentrations in serum samples from children with asthma (ages <1 through 5 years, 6 through 10 years, and 11 through 15 years) and compared the results with those in children with APBA and adults with asthma. The use of an indirect amplified ELISA with Af adsorbed to microtiter wells demonstrated that serum samples from children with ABPA have elevated IgE-Af, IgG-Af, and IgA-Af concentrations compared with those in serum samples from children with asthma. The assays were sensitive and highly specific in discriminating ABPA from asthma in children. Isotypic antibodies to Af in children do not demonstrate age-related increases as occur for total serum IgE, IgG, and IgA concentrations. Use of serum samples from patients with adult asthma instead of those from children with asthma decreases the sensitivity of assays for IgA-Af and IgG-Af in terms of identifying cases of ABPA. As a group, adults with asthma have increased serum IgE-Af concentrations when compared with children with asthma, despite having threefold to 10-fold lower concentrations of total serum IgE. The results from this study emphasize the essentiality of using age-appropriate control serum in in vitro assays and demonstrate the utility of an ELISA system for serodiagnosis of ABPA in children.