Aspergillus fumigatus components distinguish IgE but not IgG4 profiles between fungal sensitization and allergic broncho-pulmonary aspergillosis

Abstract

Aspergillus fumigatus is the causative agent of allergic broncho-pulmonary aspergillosis. Prompt and accurate diagnosis may be difficult to achieve with current clinical and laboratory scores, which do not include immune responses to recombinant A. fumigatus allergens. We measured specific immunoglobulin E and G4 directed to recombinant A. fumigatus allergens in 55 cystic fibrosis patients without allergic broncho-pulmonary aspergillosis but sensitized to A. fumigatus and in nine patients with allergic broncho-pulmonary aspergillosis (two with cystic fibrosis and seven with asthma). IgG4 responses to recombinant A. fumigatus allergens were detected in all patients, but neither prevalence nor levels were different between the two patient groups. On the other hand, both prevalence and levels of IgE responses to Asp f 3, Asp f 4, and Asp f 6 helped distinguish allergic broncho-pulmonary aspergillosis from A. fumigatus sensitization with good negative and positive predictive values.

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

“…Current reports on IgG responses to commercially available allergens from A. fumigatus are scarce and address mainly ABPA patients with an asthmatic background . Our team found that IgG4 responses to A. fumigatus allergens did not distinguish between A. fumigatus ‐sensitized CF patients and active ABPA . A first step toward an integrated IgE and IgG workup might be the use of a single method for head‐to‐head comparison.…”

“…This explains the tentative proposal of “a raised level of sIgE to A. fumigatus ” in more recent papers. Abundant experimental data support this view, but a widely validated threshold is lacking. Disparate cutoff values have been reported in the literature, from 1.91 kUA/L to “class 2 or more” to 29.8 kUA/L .…”

“…In less than a decade, component‐resolved diagnostics revolutionized diagnostic accuracy, therapeutic choice, follow‐up criteria, and prognostic prediction in allergic diseases . Some of these proteins are currently under investigation for a combined follow‐up of IgE and IgG responses, both in humoral and in cellular assays with basophil activation tests . Although their prophylactic and curative therapeutic use is intensively investigated, allergenic proteins are currently available only for in vitro procedures.…”

“…Sensitization and raised levels of IgE to secreted Asp f 1 and to somatic Asp f 2 have been reported in 60%‐100% of patients with ABPA and in 45%‐75% of “benign” Aspergillus sensitization or other aspergillosis clinical presentations . As a result, detection of IgE to Asp f 1 or Asp f 2 cannot identify patients with ABPA.…”

“…For all allergens, further information is provided by quantitative comparison of IgE responses to individual A. fumigatus molecular allergens . In this case, threshold levels depend on the control population, that is, healthy controls, asthmatic or CF patients, and therefore need validation prior to use in a given population of patients.…”