Gliotoxin and bis(methylthio)gliotoxin are not reliable as biomarkers of invasive aspergillosis

Mycoses. 2019 Oct;62(10):945-948. doi: 10.1111/myc.12967. Epub 2019 Aug 12.

Abstract

Background: Invasive pulmonary aspergillosis (IPA) remains a life-threatening opportunistic infection, but can be difficult to diagnose. New biomarkers are therefore needed. Gliotoxin (GT), a secondary metabolite of Aspergillus fumigatus, and bis(methylthio)gliotoxin (bmGT), a degradation product of GT, have been proposed as potential biomarkers. However, these findings have yet to be confirmed.

Objectives: To identify the diagnostic potential of GT and bmGT in serum and bronchoalveolar lavage fluid (BALf) in haematology patients compared to galactomannan (GM).

Materials and methods: We prospectively collected culture supernatant, serum and BALf from patients with culture-positive IPA and measured GT and bmGT concentrations using ultra high-performance liquid chromatography-quadrupole time of flight mass spectrometry. Galactomannan was detected using a commercially available enzyme immunoassay.

Results: We included 18 patients with proven (n = 6) and probable (n = 12) IPA, all with positive cultures for Aspergillus fumigatus. BmGT was only detected in serum from one patient (5.6%), whereas GM was positive (optical density ≥ 0.5) in 11/18 patients (61.1%, P = 0.002). We could not find GT in any serum sample. In BALf, bmGT was detected in 8/18 patients (44.4%) and GT in 9/18 patients (50%), compared to GM (optical density ≥ 1.0) in all patients (100%).

Conclusions: Gliotoxin and bis(methylthio)gliotoxin had a very poor performance for diagnosing IPA. As other biomarkers are more sensitive and easier to detect, we would not recommend serum or BALf GT/bmGT to be used in the diagnosis of IPA.

Keywords: Aspergillus fumigatus; bis(methylthio)gliotoxin; diagnosis; gliotoxin; invasive aspergillosis.

MeSH terms

  • Biomarkers / blood*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Diagnostic Tests, Routine / methods*
  • Galactose / analogs & derivatives
  • Gliotoxin / analogs & derivatives*
  • Gliotoxin / blood*
  • Humans
  • Invasive Pulmonary Aspergillosis / diagnosis*
  • Mannans / blood
  • Prospective Studies
  • Serum / chemistry

Substances

  • Biomarkers
  • Mannans
  • bis(methylthio)gliotoxin
  • galactomannan
  • Gliotoxin
  • Galactose