A multiplexed and miniaturized serological tuberculosis assay identifies antigens that discriminate maximally between TB and non-TB sera

J Immunol Methods. 2005 Jun;301(1-2):154-63. doi: 10.1016/j.jim.2005.04.004.

Abstract

We have developed a multiplexed and miniaturized TB serological assay with the aim of identifying (combinations of) antigens that maximally discriminate between TB and non-TB patients. It features a microarray accommodating 54 TB antigens, less than 1 microl serum consumption and an indirect immunofluorescence detection protocol. With a panel of 20 TB and 80 non-TB sera we ranked combinations of TB antigens with respect to sensitivity and specificity of TB detection by means of logistic step-forward regression analysis. The highest-ranking TB antigen combination had an area-under-the-curve of the receiver-operator-characteristics (ROC) of 0.95. We also identified an antigen that on its own provided good specificity and sensitivity of TB detection (Ara6-BSA; area-under-the-ROC curve: 0.90). These area-under-the-ROC curve values are exceptionally high for a serological TB assay. We conclude that TB antigen microarrays permit rapid identification of TB antigens that, either alone or in combination, discriminate maximally between TB and non-TB patients and that such identification provides an excellent starting point for developing point-of-care diagnostic assays.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Bacterial / immunology
  • Antibody Specificity
  • Antigens, Bacterial / immunology*
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Humans
  • Immune Sera / immunology*
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / immunology*
  • Oligosaccharides / chemistry
  • Oligosaccharides / metabolism
  • Protein Array Analysis
  • ROC Curve
  • Sensitivity and Specificity
  • Serologic Tests / methods*
  • Tuberculosis / blood*
  • Tuberculosis / diagnosis
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Immune Sera
  • Oligosaccharides