UTILITY OF IMMUNODIAGNOSTICS FOR DIFFERENT SYNDROMES CAUSED BY ASPERGILLUS

Kieren A, Marr, MD

Author address: 

Johns Hopkins University, USA

Abstract: 

Aspergillus species cause a spectrum of illnesses, ranging from allergic to invasive diseases. The type of syndrome is largely defined by the hosts’ immune response to the fungus in the airway or in tissues. When considering that the syndrome itself is a combined function of both fungal factors and the host’s response, it makes sense that diagnostics have evolved to include both the measurement of fungal factors, and variables that describe the hosts’ immune response. This is particularly important, as Aspergillus species can be present in the airways, and perhaps even in other tissues, without causing disease. This presentation will discuss the utility of immunodiagnostics, specifically, measurement of Aspergillus-specific antibody responses and cellular immunity, in predicting allergic and invasive aspergillosis, with consideration of the immunopathogenesis of disease.Our current understanding of the pathogenesis of disease is that inhaled conidia are cleared from the airway on an ongoing basis, by resident phagocytic cells (epithelial cells, macrophages) that do not generate inflammatory responses unless they sense organisms of a more mature morphotype (swollen conidia / hyphae). Recognition of these more mature forms generates a cascade that triggers acute inflammation and induces an environment in which antigen presenting cells mature to a distinct phenotype, effectively tailoring cellular immunity. New data show that specific antigens- proteases- may be processed by different cells, basophils, instructing allergenic properties. Thus, the nature of B cell and T cell responses specifically, the promotion of specific antibodies and type of cellular immunity (Th1-Th2-Th17) is a combined function of the nature of antigens produced by the fungus, as well as the inflammatory environment tailored by the presence or absence of specific pathogen associated molecules, and the hosts’ genetic make-up. Historically, we have appreciated that people with allergic aspergillosis produce Aspergillus-specific IgG and IgE to multiple allergenic proteins. These allergens are also recognized by CD4+ T cells that have a Th2 phenotype. More recently, data suggest that healthy, non-allergic people demonstrate antibody responses to multiple Aspergillus "œallergens", and they have circulating CD4+ T cells with variable cytokine expression profiles; baseline cellular immunity is variable, even in a healthy population. These responses may be important when considering risks for both allergic- and invasive disease after secondary immunosuppression. It is likely that the nature, and extent of Aspergillus-specific cellular immunity is dictated both by the hosts’ efficacy in clearing airway conidia (effectively limiting exposure to hyphal excreted allergenic proteins), and by other genetic variables that dictate early and late inflammatory responses. For this reason, measurement of antibody and/or specific cellular immunity may allow us to identify peoplewith high risks for both allergic and invasive aspergillosis.
2010

abstract No: 

none

Full conference title: 

4th Advances Against Aspergillosis
    • AAA 4th (2010)