Molecular‐based allergy diagnosis of allergic bronchopulmonary aspergillosis in Aspergillus fumigatus‐sensitized Japanese patients

Abstract

SummaryBackgroundDistinguishing between patients with allergic bronchopulmonary aspergillosis (ABPA) and Aspergillus fumigatus (Af)‐sensitized asthmatic patients without ABPA is sometimes difficult owing to the IgE‐cross‐reactivity between Af and other fungal allergens.ObjectiveTo establish the usefulness of molecular‐based allergy diagnostics using allergen components from Af in distinguishing ABPA from Af‐sensitized asthma without ABPA.MethodsSera from Japanese patients with ABPA (n = 53) and Af‐sensitized asthma without ABPA (n = 253) were studied. The levels of IgE and IgG antibodies to allergen components from Af and IgE antibodies to different fugal allergen extracts were measured by ImmunoCAP. Comorbid atopic dermatitis (AD) was taken into consideration in the sensitization profile analysis.ResultsPatients with ABPA possessed significantly higher levels of IgE antibodies to Asp f 1, and Asp f 2 than asthmatic patients without ABPA. The areas under the receiver operating characteristic curves for the levels of IgE to Asp f 1 and Asp f 2 as diagnostic markers of ABPA were 0.75 and 0.78, respectively. The presence of IgE positivity to Asp f 1 and/or Asp f 2 resulted in increased sensitivity while losing little specificity. Comorbid AD was associated with higher levels of IgE to Asp f 6 (manganese superoxide dismutase from Af, a ubiquitous pan‐allergen in fungi) and low but positive levels of IgE to other Af‐components, which hampered the serological discrimination of ABPA.Conclusions and Clinical RelevanceThe levels of IgE to Asp f 1 and/or Asp f 2 can effectively differentiate ABPA from Af‐sensitized asthma, suggesting that the amounts of IgE specific for these molecules are markers for genuine Af‐sensitization in ABPA. However, comorbid AD must be taken into consideration in the interpretation of high IgE to Asp f 6. Establishing of IgE‐sensitization profiles using panel of Af‐allergen components provides valuable information for distinguishing genuine vs. cross‐reactive sensitization in Af‐sensitized patients.

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 .…”

“…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 .…”

“…It comes with an abundant literature of IgE skin prick test and IgE clinical diagnosis correlates . Moreover, it allows the determination of other antibody class responses (IgG, IgG4, IgA) with the same technical performances . This method requires a minute volume of serum or plasma (40 μL) for assaying one specificity, that is, 240 μL for a complete A. fumigatus extract and determination of five allergens.…”

“…Some reports on Asp f 3, Asp f 4, and Asp f 6 warned against their cross‐reactivity with homologues from other fungi, which should be considered during comorbid atopic dermatitis . However, assessing sensitization to the complete panel of A. fumigatus allergens should avoid misinterpretation.…”

“…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.…”