Detection of bismethyl Gliotoxin in serum from patients with probable aspergillosis : validation of the biomarker and development of an ELISA test

Ref ID: 19503

Author:

MP Domingo1,2, M Vidal3, D Nuñez1,2, MJ Revillo3, L Roc3, JF Meis4,5, R Wallich6, A Rezusta3,
EM Galvez1, J Pardo2,7,8*

Author address:

1Procesos Quimicos y Nanotecnologí­a, Instituto de Carboquí­mica ICB-CSIC, Zaragoza, Spain
2Dpto. Bioquí­mica y Biologí­a Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain
3Microbiologí­a, Hospital Universitario Miguel Servet, IIS Aragón, Za

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose: Invasive aspergillosis (IA) is the most common nosocomial opportunistic infection caused by
pathogens of the genus Aspergillus (mainly by Aspergillus fumigatus) that occurs in patients who
are severely immunosuppressed and carries a high mortality. This is due in part to the absence of
optimal diagnostic modalities, which hamper early specific disease detection. We have previously
shown that the secondary metabolite bis(methylthio)gliotoxin (bmGT) is detected in serum from
patients with possible and probable aspergillosis. It is the aim of this study to monitor the presence
of bmGT in sequential series of serum with possible/probable and proven IA and develop an ELISA
kit to monitor the presence of this biomarker in serum from patients at risk of IA.
Methods:
A mAb against bmGT has been produced in mice and the conditions for its use in ELISA have
been optimised. The presence of bmGT in sequential series of serum from patients at risk of IA
(retrospective and prospective samples) or with proven aspergillosis (retrospective samples) is
simultaneously analysed by chromatography and ELISA test and compared to the GMN index.
Results:
We have established a fast and sensitive ELISA test for bmGT detection in human serum. The
specificity of this test has been validated in serum samples as well as in cell cultures of different
Aspergillus strains including those that do not produce bmGT. In most cases we found a good
correlation between bmGT and GMN values indicating that bmGT is a useful biomarker to confirm
GMN positive values. However, in some samples either GMN or bmGT is negative. Preliminary
analyses suggest that in some cases, in which sporadic GMN positives are found in patients, bmGT
detection could be very useful to avoid false positives. Of note bmGT is detected earlier than GMN
in some cases suggesting that it may be an early diagnosis biomarker. In addition, we have found that
bmGT concentration drops faster than GMN index when therapeutic concentrations of voriconazole
are found in serum. Finally the ELISA test is able to differentiate patients containing bmGT and
GMN in serum from those that do not present biochemical evidences of infection.
Conclusion:
Detection bmGT in serum for patients at risk of IA would complement GMN index in order to
improve diagnosis of IA. Moreover, our data suggest that by including determination of bmGT in
routine management of patients at risk of IA we could improve the rate of false negative and false
positive cases due to GMN determination. Our data provide the basis for the implementation of the
bmGT ELISA test as routine Aspergillus diagnostics in clinical laboratories.

Abstract Number: 31

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

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