Prospective study of the serum Aspergillus-specific IgG, IgA and IgM assays for chronic pulmonary aspergillosis diagnosis

Xiuqing Ma, Kaifei Wang, Xin Zhao, Yang Liu, Yanqin Li, Xiaotian Yu, Chunsun Li, David W Denning, Lixin Xie, Xiuqing Ma, Kaifei Wang, Xin Zhao, Yang Liu, Yanqin Li, Xiaotian Yu, Chunsun Li, David W Denning, Lixin Xie

Abstract

Background: Chronic pulmonary aspergillosis (CPA) is an underdiagnosed and misdiagnosed disease and now increasingly recognised. However, the diagnosis of CPA remains challenging. In this study, we aimed to investigate the diagnostic values of serum Aspergillus-specific IgG, IgA and IgM antibodies in patients with CPA.

Methods: The prospective study was performed at Chinese People's Liberation Army General Hospital in Beijing, from January 2017 to December 2017. Adult patients with lung lesions presented as cavity, nodule, mass, bronchiectasis or severe fibrotic destruction with at least two lobes in CT imaging were enrolled. One hundred healthy persons were also enrolled as additional controls. The serum levels of Aspergillus-specific IgG, IgA and IgM antibodies and galactomannan (GM) levels were measured simultaneously by plate ELISA kit.

Results: A total of 202 patients were enrolled in this study, including 42 CPA patients, 60 non-CPA patients and 100 healthy persons. The most common underlying lung diseases in CPA patients were bronchiectasis (28.6%) and COPD (19.0%). The most common symptoms in the CPA patients were cough (76.2%), sputum (71.4%), and fever (45.2%); chest pain (4.8%) was infrequent. Receiver operating characteristic (ROC) curve analysis revealed that the optimal CPA diagnostic cut-off of Aspergillus-specific IgG, IgA and IgM assays and GM test were 89.3 AU/mL, 8.2 U/mL, 73.3 AU/mL and 0.5μg/L, respectively. The serum levels of Aspergillus-specific IgG and IgA in CPA patients were higher than these in non-CPA patients or healthy persons. The sensitivities and specificities of Aspergillus-specific IgG, IgA, IgM tests and GM test were 78.6 and 94.4%, 64.3 and 89.4%, 50.0 and 53.7% and 71.4 and 58.1%, respectively.

Conclusions: The sensitivity and specificity of serum Aspergillus-specific IgG assay are satisfactory for diagnosing CPA, while the performance of Aspergillus-specific IgA assay is moderate. Aspergillus-specific IgM assay and serum GM test have limited value for CPA diagnosis.

Trial registration: NCT03027089 . Registered 20 January 2017.

Keywords: Aspergillus-specific IgA antibody; Aspergillus-specific IgG antibody; Aspergillus-specific IgM antibody; Chronic pulmonary aspergillosis; Galactomannan.

Conflict of interest statement

Xiaotian Yu received an educational and post-doctoral funding from Dynamiker Limited. The remaining authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Representative examples of CT appearances in patients with CPA. CT images show: a a small fungus ball with an air crescent sign in the right upper lobe (b) aspergillus nodule with cavitary lesions and halo sign in the right upper lobe, c reticular pattern of inflammatory or fibrotic change surround small lung bullae and areas of consolidation and some pleural thickening and indrawing of fat in the right upper lobe, d consolidaton, with multiple nodules and marked loss of volume in the left lung, e bronchiectasis in the right upper and lower lobe and left lower lobe, f bronchiectasis and inflammatory infiltrates in both lower lobes, g consolidation in the right middle lobe, irregular nodule with surrounding ground glass in the right lower lobe and bilateral pleural effusions, h aspergillus nodules in both lower lobes and reticular pattern in the left upper lobe
Fig. 2
Fig. 2
Comparisons of CRP concentration, WBC count, neutrophil percentage, and lymphocyte percentage in peripheral blood between CPA and non-CPA patients. The p-Values were: a, 0.229; b, 0.398; c, 0.500; d, 0.151, respectively. Mean and standard error are shown
Fig. 3
Fig. 3
ROC analysis for CPA patients, non-CPA patients and healthy controls. The AUC of Aspergillus IgG, IgA, IgM assays and GM test were 0.915 (95% CI, 0.860 to 0.969), 0.833(95% CI, 0.764 to 0.903), 0.488 (95% CI, 0.391to 0.584), 0.622 (95% CI, 0.527 to 0.716) respectively
Fig. 4
Fig. 4
Average Aspergillus IgG (a), IgA (b) and IgM (c) level and GM (d) in serum from healthy control group, non-CPA group and CPA group. Data represent the means±SDs

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