Cut-Offs and Diagnostic Performance of IgG Against Recombinant Aspergillus fumigatus Antigens in Differentiating ABPA From Asthma

Abstract

Background: The diagnostic cut-off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA) remain unclear.

Objectives: To derive and validate diagnostic cut-offs for IgG antibodies against rAsp f 1, f 2 and f 4 in ABPA and assess their diagnostic performance in distinguishing ABPA from asthma.

Methods: In this case-control study, we prospectively enrolled consecutive subjects with asthma and ABPA. We measured serum IgG levels against rAsp f 1, rAsp f 2 and rAsp f 4 using a fluorescent enzyme immunoassay. Subjects were randomly split into derivation (50%) and validation (50%) cohorts. Cut-offs were derived using receiver operating characteristic (ROC) curves and Youden's index. Additionally, we performed Bayesian latent class analysis (BLCA) using two-component Gaussian mixture models to derive unbiased cut-offs. Diagnostic performance was assessed using sensitivity, specificity and the area under the ROC curve (AUROC).

Results: Of 375 participants, 261 had ABPA and 114 had asthma. ROC-derived AUROC values for rAsp f 1, f 2 and f 4-IgG were 0.63, 0.47 and 0.52, while the cut-off values were 10.1 mgA/L, 10.3 mgA/L and 10.5 mgA/L, respectively. Sensitivity was ≤ 42% for all antigens, while specificity exceeded 89%. BLCA yielded cut-offs of 18.6, 14.9 and 13.7 mgA/L for f 1, f 2 and f 4, respectively, with similarly poor sensitivity and high specificity.

Conclusions: IgG antibodies against rAsp f 1, f 2 and f 4 exhibit high specificity but poor sensitivity in identifying ABPA, limiting their utility as standalone diagnostic markers.

Keywords: allergic bronchopulmonary mycosis; allergy; aspergillus; asthma; bronchiectasis.