Journal of Molecular Medicine

, Volume 85, Issue 6, pp 613–621

Candidate biomarkers for discrimination between infection and disease caused by Mycobacterium tuberculosis

Authors

    • Department of ImmunologyMax Planck Institute for Infection Biology
  • Dirk Repsilber
    • Institute for Medical Biometry and StatisticsUniversity at Lübeck
    • Institute for Biochemistry and BiologyUniversity Potsdam
  • Andrea Gutschmidt
    • Department of ImmunologyMax Planck Institute for Infection Biology
  • Albert Neher
    • Asklepios Center for Respiratory Medicine and Thoracic Surgery
  • Knut Feldmann
    • Asklepios Center for Respiratory Medicine and Thoracic Surgery
  • Hans J. Mollenkopf
    • Microarray Core FacilitiesMax Planck Institute for Infection Biology
  • Andreas Ziegler
    • Institute for Medical Biometry and StatisticsUniversity at Lübeck
  • Stefan H. E. Kaufmann
    • Department of ImmunologyMax Planck Institute for Infection Biology
Original Article

DOI: 10.1007/s00109-007-0157-6

Cite this article as:
Jacobsen, M., Repsilber, D., Gutschmidt, A. et al. J Mol Med (2007) 85: 613. doi:10.1007/s00109-007-0157-6

Abstract

Infection with Mycobacterium tuberculosis is controlled by an efficacious immune response in about 90% of infected individuals who do not develop disease. Although essential mediators of protection, e.g., interferon-γ, have been identified, these factors are insufficient to predict the outcome of M. tuberculosis infection. As a first step to determine additional biomarkers, we compared gene expression profiles of peripheral blood mononuclear cells from tuberculosis patients and M. tuberculosis-infected healthy donors by microarray analysis. Differentially expressed candidate genes were predominantly derived from monocytes and comprised molecules involved in the antimicrobial defense, inflammation, chemotaxis, and intracellular trafficking. We verified differential expression for alpha-defensin 1, alpha-defensin 4, lactoferrin, Fcγ receptor 1A (cluster of differentiation 64 [CD64]), bactericidal permeability-increasing protein, and formyl peptide receptor 1 by quantitative polymerase chain reaction analysis. Moreover, we identified increased protein expression of CD64 on monocytes from tuberculosis patients. Candidate biomarkers were then assessed for optimal study group discrimination. Using a linear discriminant analysis, a minimal group of genes comprising lactoferrin, CD64, and the Ras-associated GTPase 33A was sufficient for classification of (1) tuberculosis patients, (2) M. tuberculosis-infected healthy donors, and (3) noninfected healthy donors.

Keywords

Mycobacterium tuberculosisTuberculosisBiomarkers

Supplementary material

109_2007_157_MOESM1_ESM.xls (82 kb)
Supplementary Table S2Top 95 candidate genes from microarray comparisons between TB patients and latently M. tuberculosis infected healthy contacts (XLS 84 kb)

Copyright information

© Springer-Verlag 2007