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.
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Acknowledgments
This study was supported in part by the National Genome Research Network (Germany), the EU FP6 funded IP “TBVAC”, and Grand Challenge 6 of the Bill & Melinda Gates Foundation to S. H. E. Kaufmann and M. Jacobsen. H.-J. Mollenkopf and S. H. E. Kaufmann acknowledge additional funding by the European Fund for Regional Development/State of Berlin. The authors have no conflicting financial interests. We thank M. L. Grossman for carefully revising the manuscript.
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Supplementary Table S2
Top 95 candidate genes from microarray comparisons between TB patients and latently M. tuberculosis infected healthy contacts (XLS 84 kb)
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Jacobsen, M., Repsilber, D., Gutschmidt, A. et al. Candidate biomarkers for discrimination between infection and disease caused by Mycobacterium tuberculosis . J Mol Med 85, 613–621 (2007). https://doi.org/10.1007/s00109-007-0157-6
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DOI: https://doi.org/10.1007/s00109-007-0157-6