Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and molecular diagnostics in allergic bronchopulmonary aspergillosis

Abstract

A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe A. fumigatus-related diseases due to possible evolution toward pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asth- | ASPERGILLUS FUMIGATUS AND ITS INTERACTION WITH THE HUMAN HOSTThe Aspergillus genus comprises 339 species of filamentous fungi ubiquitous all over the world in human environment, for example, air, soil, cereals, fruit, plants, wet and decomposing organic matter.Airborne Aspergillus spp spores are present indoors and outdoors, with an estimated 10-1000 spores inhaled daily by each human. 4,5 A growing number of Aspergillus species are recognized as pathogenic for animals and humans; yet A. fumigatus (Figure 1) The pathophysiological continuum of A. fumigatus-host interaction is mirrored by laboratory and clinical frames of "asymptomatic"colonization, "benign" IgE sensitization to A. fumigatus, through A. fumigatus-induced cough and asthma, to aspergilloma and invasive aspergilloses. However, the first two stages lack consensus definitions. The growth of A. fumigatus in the airways, also termed "car- irreversible, calls for updating the immunological criteria have been accumulating since the turn of the century. 47,52,60 These calls are supported by novel tools with enhanced performance.We will describe hereafter the issues associated with the current ABPA immunological diagnostic criteria including total serum IgE,A. fumigatus-specific IgE, and A. fumigatus-specific IgG and precipitins against A. fumigatus.

Diagnostic markers of allergic bronchopulmonary aspergillosis in patients with severe asthma

“…The important pre‐disposing to ABPA factor is the presence of fungi within the airways of the patients with asthma or cystic fibrosis (CF) 8‐10 . A fumigatus conidia are recognised via Toll‐like receptors on dendritic cells and airway epithelial cells, leading to production of TSLP, IL‐33, IL‐25 10,11 . Pivotal role of allergic inflammation is associated with TSLP.…”

“…Proteases secreted by A fumigatus activate proteinase‐activated receptors (PARs) and enhance secretion of IL‐8 in airway epithelial cells 10 . Gibsonat et al 18 found that the neutrophil chemoattractant, IL‐8, was elevated in ABPA, and therefore suggested that IL‐8 promotes neutrophil influx and activation.…”

The complex role of mast cells in fungal infections

“…[40][41][42] ABPA is associated with early allergic and late-phase inflammatory responses of the lungs to A. fumigatus antigens that occur in a minority (less than 1%) of patients with asthma and, more often (7%-10%), in patients with cystic fibrosis. [43] ABPA ways. [44][45][46] Proteases released from MCs can promote the release of growth factors from airway epithelial cells driving strong and irreversible remodelling reactions in airways of patients with ABPA, resulting in bronchiectasis lesions and fibrosis.…”

A new IgE Western blot identifies Aspergillus fumigatus sensitization and may discriminate allergic bronchopulmonary aspergillosis

“…1,2 Allergic bronchopulmonary aspergillosis (ABPA) is a severe ARD, with an estimated prevalence of 2.5% among asthmatic patients and up to 15% among patients with CF. 3 The detection of Af-specific IgE (Af-IgE) through serological or skin tests defines Af sensitization, a common finding in patients with asthma or CF. 2,4,5 A "raised" level of Af-IgE is a major ABPA diagnostic criterion, 6 but the definition of "raised" IgE is still lacking.…”

“…2,3 However, discerning ABPA-related "raised" IgE from non-ABPA Af sensitization is crucial for ABPA identification, staging, and treatment choice aiming at preventing lung function deterioration. 2,3,7 Molecular allergen profiling brought more accurate IgE analysis, 7,8 but only 5/23 characterized Af allergens are currently commercialized. 9 An alternative approach using western blot (WB) would enable one-step characterization of sensitization to a greater number of Af molecules.…”