Detection of urinary excreted fungal galactomannan-like antigens for diagnosis of invasive aspergillosis

Simon F. Dufresne, Kausik Datta, Xinming Li, Ekaterina Dadachova, Janet F. Staab, Thomas F. Patterson, Marta Feldmesser, Kieren A. Marr

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Mortality associated with invasive aspergillosis (IA) remains high, partly because of delayed diagnosis. Detection of microbial exoantigens, released in serum and other body fluids during infection, may help timely diagnosis. In course of IA, Aspergillus galactomannan (GM), a well established polysaccharide biomarker, is released in body fluids including urine. Urine is an abundant, safely collected specimen, well-suited for point-of-care (POC) testing, which could play an increasing role in screening for early disease. Our main objective was to demonstrate GM antigenuria as a clinically relevant biological phenomenon in IA and establish proof-of-concept that it could be translated to POC diagnosis. Utilizing a novel IgM monoclonal antibody (MAb476) that recognizes GM-like antigens from Aspergillus and other molds, we demonstrated antigenuria in an experimental animal IA model (guinea pig), as well as in human patients. In addition, we investigated the chemical nature of the urinary excreted antigen in human samples, characterized antigen detection in urine by immunoassays, described a putative assay inhibitor in urine, and indicated means of alleviation of the inhibition. We also designed and used a lateral flow immunochromatographic assay to detect urinary excreted antigen in a limited number of IA patient urine samples. In this study, we establish that POC diagnosis of IA based on urinary GM detection is feasible. Prospective studies will be necessary to establish the performance characteristics of an optimized device and define its optimal clinical use.

Original languageEnglish (US)
Article numbere42736
JournalPLoS One
Volume7
Issue number8
DOIs
StatePublished - Aug 10 2012

Fingerprint

Aspergillosis
aspergillosis
antigens
urine
Antigens
Urine
Aspergillus
Body fluids
Point-of-Care Systems
Assays
body fluids
Body Fluids
Molds
Biomarkers
microbial detection
exoantigens
Immunochromatography
Polysaccharides
Immunoglobulin M
Biological Phenomena

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Dufresne, S. F., Datta, K., Li, X., Dadachova, E., Staab, J. F., Patterson, T. F., ... Marr, K. A. (2012). Detection of urinary excreted fungal galactomannan-like antigens for diagnosis of invasive aspergillosis. PLoS One, 7(8), [e42736]. https://doi.org/10.1371/journal.pone.0042736

Detection of urinary excreted fungal galactomannan-like antigens for diagnosis of invasive aspergillosis. / Dufresne, Simon F.; Datta, Kausik; Li, Xinming; Dadachova, Ekaterina; Staab, Janet F.; Patterson, Thomas F.; Feldmesser, Marta; Marr, Kieren A.

In: PLoS One, Vol. 7, No. 8, e42736, 10.08.2012.

Research output: Contribution to journalArticle

Dufresne, SF, Datta, K, Li, X, Dadachova, E, Staab, JF, Patterson, TF, Feldmesser, M & Marr, KA 2012, 'Detection of urinary excreted fungal galactomannan-like antigens for diagnosis of invasive aspergillosis', PLoS One, vol. 7, no. 8, e42736. https://doi.org/10.1371/journal.pone.0042736
Dufresne, Simon F. ; Datta, Kausik ; Li, Xinming ; Dadachova, Ekaterina ; Staab, Janet F. ; Patterson, Thomas F. ; Feldmesser, Marta ; Marr, Kieren A. / Detection of urinary excreted fungal galactomannan-like antigens for diagnosis of invasive aspergillosis. In: PLoS One. 2012 ; Vol. 7, No. 8.
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