Antibody Responses to <i>Aspergillus fumigatus</i> Allergens in Patients with Cystic Fibrosis

Aspergillus fumigatus Cystic fibrosis Allergic bronchopulmonary aspergillosis Itraconazole Correspondence to: Dr. L. Karla Arruda, Asthma and Allergic Diseases Center, Box 225, University of Virginia, Charlottesville, VA 22908 (USA) Introduction Fungi of the genus Aspergillus are associated with a spectrum of human diseases including asthma, allergic bronchopulmonary aspergillosis (ABPA), aspergilloma and cystic fibrosis (CF). We have previously reported that CF patients have a significantly higher prevalence of IgE antibody (Ab) to Aspergillus fumigatus (60%) than patients with asthma (6%). In addition, most CF patients (84%) had serum IgG Ab to A.fumigatus allergen Asp f 1. A subset of CF patients fulfilled the immunologic criteria for ABPA, including some children < 5 years old [1]. Asp f 1, whichs is a major \8-kO A. fumigatus allergen, is a member of the mito-gillin family of cytotoxins [2]. The complete nucleotide sequence of Asp f 1 has been determined [3], and recombinant Asp f 1 with IgE-binding activity has been produced [4]. In addition, Asp f 1 causes proliferative T cell responses in patients with ABPA [5]. Our studies suggested that CF patients are frequently colonized with A.fumigatus, and that this colonization may contribute to the lung damage in some CF patients. Methods and Results We have extended the analysis of A. fumigatus IgG and IgE Ab responses to a group of 119 CF patients (age 10 months^-6 years). IgG Ab was measured by antigen-binding RIA using 125Ilabeled Asp f 1, and IgE Ab to A. fumigatus was quantitated by radioallergosorbent test. Eightynine percent of the patients had detectable IgG to Asp f 1, and 14% fulfilled the immunologic criteria forABPA. The RIA using l25I-labeled Asp f 1 was also used to monitor IgG Ab levels following antifungal therapy. Treatment of two CF patients with itraconazole over periods of 7 and 12 months resulted in a significant decrease in IgG Ab levels. In addition, a 6-year follow-up of a patient who presented with invasive aspergilloma and who was treated with surgery and amphotericin B [6] has shown a steady decrease (up to 65%) in the levels of IgG Ab to Asp f 1.