Antibody specific to thioredoxin reductase as a new biomarker for serodiagnosis of invasive aspergillosis in non-neutropenic patients

Clin Chim Acta. 2012 May 18;413(9-10):938-43. doi: 10.1016/j.cca.2012.02.011. Epub 2012 Feb 17.

Abstract

Background: Invasive aspergillosis (IA) is an important cause of mortality in critically ill patients, but the diagnosis is difficult as clinical and radiological signs are neither sensitive nor specific. Serum galactomannan (GM) is a useful marker for IA, but exhibits low sensitivity in non-neutropenic patients. In our previous work, strong antibody reactivity to thioredoxin reductase of Aspergillus fumigatus was found in non-neutropenic IA patients.

Methods and results: Using recombinant thioredoxin reductase GliT (TR), an antigenic protein secreted by A. fumigatus, as the coating antigen, an enzyme-linked immunosorbent assay (ELISA) for detecting anti-TR antibodies was developed. The antibody response to TR in IA animal models and 42 non-neutropenic patients with culture- and/or histology-documented IA was investigated. The results showed that anti-TR antibody was detectable in rabbit serum 7-9 days after exposure to the fungus. The sensitivity and specificity of the anti-TR antibody assay in patients were 80.9% and 96%, respectively, while the sensitivity of GM in this group of patients was only 52.3%. The specificity of the assay was confirmed by testing the sera from patients infected with other pathogenic fungal species and bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antibodies, Fungal / blood*
  • Antibody Specificity*
  • Aspergillosis / blood*
  • Aspergillosis / diagnosis
  • Biomarkers / blood
  • Enzyme-Linked Immunosorbent Assay / methods
  • Enzyme-Linked Immunosorbent Assay / standards
  • Female
  • Galactose / analogs & derivatives
  • Humans
  • Male
  • Mannans / blood
  • Middle Aged
  • Neutropenia*
  • Rabbits
  • Sensitivity and Specificity
  • Serologic Tests / methods
  • Serologic Tests / standards
  • Thioredoxin-Disulfide Reductase / blood*

Substances

  • Antibodies, Fungal
  • Biomarkers
  • Mannans
  • galactomannan
  • Thioredoxin-Disulfide Reductase
  • Galactose