1389-2037/14 $58.00+.00 © 2014 Bentham Science Publishers Allergic Aspergillosis and the Antigens of Aspergillus fumigatus Bharat Singh 1 , Seema Singh 1 , Abdul R. Asif 2 , Michael Oellerich 2 and Gainda Lal Sharma 1,* 1 CSIR-Institute of Genomics and Integrative Biology, University Campus, Mall Road, Delhi- 110007, India; 2 Department of Clinical Chemistry, University Medical Center Goettingen, Robert-Koch-Str.40, D-37075 Goettingen, Germany Abstract: Incidence of fungal infections has increased alarmingly in past few decades. Of the fungal pathogens, the As- pergillus fumigatus has been a major cause of allergic bronchopulmonary aspergillosis (ABPA) which has five main stages - the acute, remission, exacerbation, glucocorticoid dependent and fibrotic stage. The diagnosis of ABPA remains difficult due to its overlapping clinical and radiological features with tuberculosis and cystic fibrosis. From past few dec- ades, the crude fractions of A. fumigatus have been used for immunodiagnosis of ABPA. Most of the detection kits based on crude fractions of A. fumigatus are quite sensitive but have low specificity. Till date 21 known and 25 predicted aller- gens of A. fumigatus have been identified. Of these allergens, only five recombinants (rAsp f1-f4 and f6) are commer- cially used for diagnosis of allergic aspergillosis. Remaining allergens of A. fumigatus have been restricted for use in spe- cific diagnosis of ABPA, due to sharing of common antigenic epitopes with other allergens. Complete sequencing of A. fumigatus genome identified 9926 genes and the reports on the proteome of A. fumigatus have shown the presence of large number of their corresponding proteins in the pathogen. The analysis of immunoproteomes developed from crude frac- tions of A. fumigatus by IgG/IgE reactivity with ABPA patients and animal sera have identified the panel of new antigens. A brief description on the current status of A. fumigatus antigens is provided in this review. The implementation of ad- vance recombinant expression and peptidomic approaches on the A. fumigatus antigens may help in the selection of ap- propriate molecules for the development of tools for more specific early diagnosis of ABPA, and desensitization therapies for patients of allergic disorders. Keywords: Allergic aspergillosis, allergens, desensitization, diagnosis, recombinants. 1. INTRODUCTION Among the pathogenic species of Aspergillus, A. fumiga- tus is the most common cause of aspergillosis which in- cludes a spectrum of diseases. The primary route of infection by Aspergillus has been via inhalation of airborne conidia. The average size of A. fumigatus conidia has been found to be 2.0 to 3.0 μm. Because of such a small size, the conidia can easily get airborne. Also the conidial production of A. fumigatus has been highly prolific and, therefore, the human respiratory tract always remains at risk of acquiring Asper- gillus infection [1]. The germination of conidia in the respi- ratory tract and the extent of mycelial colonization in lungs has been shown to be influenced by the competence of the host immune system [2]. It was reported recently that change in temperature during the growth of A. fumigatus signifi- cantly influenced the allergenicity of A. fumigatus through differential production of allergenic proteins [3]. In upper airways, the conidia may cause respiratory discomfort due to contact irritation and allergic responses. Aimanianda et al. (2009) demonstrated that the hydrophobic nature of rodlet layer prevents immune response against dormant conidia of A. fumigatus [4]. Thus it has been suggested that the immu- nogenic responses may get induced after the release of *Address correspondence to this author at the CSIR-Institute of Genomics and Integrative Biology, University Campus, Mall Road, Delhi-110007, India; Tel: +91-11-27667439; Fax: +91-11-27667471; E-mail: drglsharma@hotmail.com cellular proteins including virulence factors and allergens from metabolically active germinating conidia. Such initial allergic reactions have been accountable for development of different forms of allergic aspergillosis. Repeated exposure of lungs to conidia, their germination, expansion of hyphal mass, and focal growth of A. fumigatus in pre-existing lung cavities such as the lesions in patients with pulmonary tuber- culosis may lead to the development of noninvasive aspergil- lomas. The A. fumigatus may invade the lung tissues and disseminate to the deeper body parts to cause systemic infec- tion. The increased severity and incidence of allergic and nonallergic aspergillosis need a better understanding of the interplay between host and fungus that contributes to A. fu- migatus pathogenesis [6]. Also, detailed knowledge of aller- genic and antigenic molecules of A. fumigatus is required for the selection of molecules for application in specific diagno- sis and immunotherapy of aspergillosis. 2. FORMS OF ASPERGILLOSIS 2.1. Allergic The A. fumigatus may cause various kinds of allergic conditions in the body of the host. These allergic reactions due to A. fumigatus may lead to the development of four distinct clinically recognizable forms of hypersensitivity respiratory disorders i.e., allergic bronchopulmonary asper- gillosis (ABPA), allergic Aspergillus sinusitis, IgE-mediated asthma, and hypersensitivity pneumonitis [5]. Send Orders for Reprints to reprints@benthamscience.net Current Protein and Peptide Science, 2014 , 15, 403-423 403