Novel Biomarkers for Invasive Aspergillosis

Aspergillosis Invasive

bis(methylthio)gliotoxin, lateral flow device, JF5, Galactomannan, Invasive aspergillosis

Diagnosis of invasive aspergillosis remains difficult, and is often based on a combination of patient characteristics, radiological and microbiological findings. To data, galactomannan (GM) is the only well-validated biomarker available. However, GM still has its shortcomings. There is therefore a need for new, complementary biomarkers. In this study, two of those tests, bis(methylthio)gliotoxin (bmGT) and a lateral flow device, will be validated in a hematological population, and compare it to GM.

Diagnosis of invasive aspergillosis is often difficult to achieve with certainty, as this requires direct evidence of invasive growth on histopathological examination. A probable diagnosis can be suspected based on both clinical and mycological evidence of the disease, in presence of a susceptible patient. The EORTC-MSG guidelines offer a widely accepted basis for this diagnosis. Under these guidelines, mycological evidence can consist of a positive culture of aspergillus spp, or of detection of galactomannan (GM) in a relevant body sample. GM is a part of the Aspergillus mould and can be detected using a commercially available immunoenzymatic sandwich microplate assay. However, like most biomarkers, galactomannan is far from a perfect biomarker. Several beta-lactam antibiotics are known to cause false positives, and anti-mould therapy has been reported to significantly lower the sensitivity\[1\]. Additional biomarkers that could circumvent these problems would therefore be beneficial. A potential new target is gliotoxin (GT), a secondary metabolite of several fungi, the most clinically important of which is Aspergillus\[2\]. GT is released during invasive growth, and can therefore be used as a biomarker of invasive fungal disease by GT-producing fungi. However, GT is quickly removed by red blood cells from circulation, making it an unreliable marker\[3\]. A degradation product of GT, bis(methylthio)gliotoxin (bmGT), appears to be more stable as it is not taken up by red blood cells. Serum bmGT or bmGT in bronchoalveolar lavage (BAL) fluid has already been shown in small studies to be a potential marker of invasive aspergillosis, especially when used in combination with GM\[3-5\]. Recently, another highly specific test has become available, based on detection of an extracellular glycoprotein secreted during the growth of Aspergillus species, using a monoclonal antibody (JF5) in an immunochromatographic lateral-flow device (LFD)\[6,7\]. This test allows fast (\<15 minutes) testing using a commercially available device. In this study, both the LFD and bmGT will be characterized and validated in a hematological population, and compared to GM.

Belgium