Bis(methyl)gliotoxin and gliotoxin in bronchoalveolar lavage fluids are not suitable markers for invasive aspergillosis
(English)Manuscript (preprint) (Other academic)
Introduction: Invasive aspergillosis is challenging to diagnose partly due to shortcomings in sensitivity, reliability, and selectivity of current diagnostic methods, which rely on cultures, assays, and histopathology. This problem may be addressed by chemical analysis of metabolites in lung fluid from infected patients. Gliotoxin and bis(methyl)gliotoxin have been pinpointed as potential marker metabolites in serum and plasma for invasive aspergillosis patients, but whether lung fluid samples could be assessed for these markers is still unknown.
Methods: Bronchoalveolar lavage samples were taken from 42 individuals with a variety of pulmonary diseases whereof 20 were diagnosed with possible invasive aspergillosis. The samples were analyzed with ultra high performance liquid chromatography coupled to triple quadropole time-of-flight mass spectrometry to investigate the use of the Aspergillus fumigatus metabolites gliotoxin and bis(methyl)gliotoxin as marker metabolites for invasive aspergillosis.
Results: Gliotoxin was not detected in any of the 42 samples, but bis(methyl)gliotoxin in 10 (24%). Bis(methyl)gliotoxin was detected in 5 (25%) of the 20 patients with possible IA and in 5 (23%) in the other 22 samples. One unknown compound (357.30 m/z) with a similar mass spectrum profile to bis(methyl)gliotoxin (357.09 m/z) was found in 32 (76%) of all samples.
Conclusions: Neither gliotoxin nor bis(methyl)gliotoxin appears to be an acceptable marker metabolite in bronchoalveolar lavage fluids for invasive aspergillosis. Further development of MS-based analyses should include chromatography.
Invasive aspergillosis, gliotoxin, bis(methyl)gliotoxin, Aspergillus fumigatus, diagnosis
Research subject Pharmacognosy
IdentifiersURN: urn:nbn:se:uu:diva-242610OAI: oai:DiVA.org:uu-242610DiVA: diva2:784271