SPECIFIC IGG(4) RESPONSES DURING CHRONIC AND TRANSIENT ANTIGEN EXPOSURE IN ASPERGILLOSIS

The factors that lead to increased production of specific IgG subclass es are still largely unknown. Recent studies suggest that increased Ig G(4) responses may be related to prolonged antigen exposure. We presen t data showing that increased IgG(4) responses are found under conditi ons of chronic exposure to Aspergillus fumigatus (Af) antigen. IgG(tot al), IgG subclass, and IgE responses were studied using ELISA, CAP-FEI A, and immunoblotting techniques in patients with pulmonary aspergillo ma (PA), which is a model for chronic antigen exposure, and allergic b ronchopulmonary aspergillosis (ABPA), characterized by transient antig en exposure. Af-IgG(1) was increased in patients with PA compared with those with ABPA. Patients with PA and IgE responses to Af and/or othe r inhalant allergens showed significantly higher Af-IgG(4) responses t han did patients with PA and negative IgE responses or patients with A BPA. Surveillance studies over time in individual patients showed conc ordance in Af-IgG(1) and Af-IgG(4) responses. Both Af-IgG(1) and Af-Ig G(4) levels followed the course of disease progression and treatment. Immunoblotting revealed correlations between Af-IgG(1) and Af-IgG(4) b inding to most, but not all, antigenic Af components. This study docum ents for the first time increased IgG(4) levels under conditions of ch ronic exposure to fungal antigen in PA. Furthermore, a significantly h igher IgG(4) response was found in those patients with PA who produced IgE. The transient exposure to Af antigen during exacerbation of ABPA gives rise to transient elevations in IgG(4) levels.