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

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.

Clinical Characteristics and Treatment Outcomes of Pathologically Confirmed Aspergillus Nodules

“…In the current guidelines, the detection of serum Aspergillus precipitin IgG antibody is a key diagnostic criterion for CPA [1,24]. Unfortunately, it is unclear whether the presence of Aspergillus IgG antibody could also be a supportive finding in the diagnosis of Aspergillus nodules.…”

Serology anno 2021—fungal infections: from invasive to chronic

“…The LFA detects GM and is licensed for serum and BAL, crossreactivity with various fungal genera exists [24], see Table 1. Head to head comparison of LFD and LFA from BALs showed identical specificity, with sensitivity and negative predictive values slightly being better for LFA [26], for more information see [30]. However, this process is slow and takes weeks to months even in improved patients; a lack of decline is suspicious of treatment failure [19].…”

Diagnostic accuracy of Aspergillus‐specific antibodies for chronic pulmonary aspergillosis: A systematic review and meta‐analysis

“…The characteristics of included studies are shown in Tables 1 and 2 below 5–11,17‐42 . Participants' characteristics varied greatly across the included studies.…”

“…Thus, the diagnostic values of Aspergillus IgA and IgM antibodies remain unclear. Since the publication of the two guidelines, 2,3 several primary studies have been published on the diagnostic test accuracy of IgA and IgM antibodies for CPA 5–9 . Moreover, a new test for the diagnosis of CPA, IgG + IgM antibody, has recently been reported 10,11 …”