Background: Infections with Aspergillus fumigatus and other moulds have been shown to induce
elevated levels of several immunologic markers. However, diagnostic potential of these markers for
invasive pulmonary aspergillosis (IPA) has not been sufficiently evaluated yet. The objective of this
study was to investigate their diagnostic performance among patients with hematological malignancies
at risk for IPA.
Material/methods: This prospective cohort study was performed between April 2014 and November
2016 at the Medical University of Graz, Austria. Adult patients with underlying hematological
malignancies and suspected pulmonary infection who underwent routine bronchoscopy were
prospectively enrolled. Cases were classified as having no, possible, probable or proven IPA using the
2008 revised EORTC/MSG criteria. After literature review the following bundle of immunologic markers
was determined: Interleukin (IL) 4, IL-6, IL-8, IL-10, IL-15, IL-17A, IL-22, soluble IL-2 receptor (sIL-2R),
tumor necrosis factor α (TNFα), interferon-γ (IFNγ) and RANTES (regulated on activation, normal T
cell expressed and secreted). Bronchoalveolar lavage fluid (BALF) samples were obtained at
bronchoscopy. In addition, corresponding serum samples were obtained within 24h of bronchoscopy.
All samples were stored at -80°C and retrospectively tested using a ProcartaPlex® 11plex
immunoassay (eBioscience, Vienna, Austria). Statistical analysis included Receiver Operating
Characteristics (ROC) curve analysis and Mann-Whitney-U-Test.
Results: After exclusion of 28 cases with possible IPA, 59 cases were included in this study (23 male,
36 female, age range: 27-82 years). Most frequently observed underlying diseases were acute
myeloid leukemia (n=19), non-hodgkin lymphoma (n=15), multiple myeloma (n=5), and acute
lymphoblastic leukemia (n=5). Two had proven and 7 probable IPA, while 50 patients had no evidence
of IPA. IL-8 was found to be significantly higher in serum and BALF samples of patients with
probable/proven IPA. In serum IL-6, IL-10 and IL-17A were also significantly elevated in these patients
(Table 1 and Figure 1). IFNγ, sIL-2R, IL-4 and RANTES showed no association with probable/proven
IPA in ROC curve analysis (each p>0.2 in serum and BALF).
Conclusions: Serum concentrations of IL-6, IL-8, IL-10 and IL-17A as well as BALF levels of IL-8
were significantly higher in patients with probable/proven IPA compared to those without evidence of
IPA. Our study indicates that these biomarkers may have diagnostic potential for diagnosing IPA
among hematological malignancy patients.
Full conference title:
- ECCMID 27th (2017)