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Human gene expression profiles of susceptibility and resistance in tuberculosis

Genes & Immunity volume 12, pages 15–22 (2011)Cite this article

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Abstract

Tuberculosis (TB) still poses a profound burden on global health, owing to significant morbidity and mortality worldwide. Although a fully functional immune system is essential for the control of Mycobacterium tuberculosis infection, the underlying mechanisms and reasons for failure in part of the infected population remain enigmatic. Here, whole-blood microarray gene expression analyses were performed in TB patients and in latently as well as uninfected healthy controls to define biomarkers predictive of susceptibility and resistance. Fc gamma receptor 1B (FCGRIB)was identified as the most differentially expressed gene, and, in combination with four other markers, produced a high degree of accuracy in discriminating TB patients and latently infected donors. We determined differentially expressed genes unique for active disease and identified profiles that correlated with susceptibility and resistance to TB. Elevated expression of innate immune-related genes in active TB and higher expression of particular gene clusters involved in apoptosis and natural killer cell activity in latently infected donors are likely to be the major distinctive factors determining failure or success in controlling M. tuberculosis infection. The gene expression profiles defined in this study provide valuable clues for better understanding of progression from latent infection to active disease and pave the way for defining predictive correlates of protection in TB.

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Acknowledgements

We thank ML Grossman for thoroughly revising the paper, J Weiner for biostatistical support and the Microarray Core Facility unit at the Max Planck Institute for Infection Biology in Berlin for sample processing. This study was funded by Grant number 37772 from the Bill & Melinda Gates Foundation through the Grand Challenges in Global Health Initiative, to all authors except DR

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Authors and Affiliations

  1. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany

    J Maertzdorf, S K Parida & S H E Kaufmann

  2. Leibniz Institute for Farm Animal Biology, Genetics and Biometry, Dummerstorf, Germany

    D Repsilber

  3. Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa

    K Stanley, T Roberts, G Black & G Walzl

Authors
  1. J Maertzdorf
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  2. D Repsilber
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  3. S K Parida
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  4. K Stanley
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  5. T Roberts
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  6. G Black
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  7. G Walzl
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  8. S H E Kaufmann
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Correspondence to J Maertzdorf or S H E Kaufmann.

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Maertzdorf, J., Repsilber, D., Parida, S. et al. Human gene expression profiles of susceptibility and resistance in tuberculosis. Genes Immun 12, 15–22 (2011). https://doi.org/10.1038/gene.2010.51

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