Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

Chloe I. Bloom, Christine M. Graham, Matthew P R Berry, Fotini Rozakeas, Paul S. Redford, Yuanyuan Wang, Zhaohui Xu, Katalin A. Wilkinson, Robert J. Wilkinson, Yvonne Kendrick, Gilles Devouassoux, Tristan Ferry, Makoto Miyara, Diane Bouvry, Valeyre Dominique, Guy Gorochov, Derek Blankenship, Mitra Saadatian, Phillip Vanhems, Huw BeynonRama Vancheeswaran, Melissa Wickremasinghe, Damien J. Chaussabel, Jacques Banchereau, Virginia Pascual, Ling pei Ho, Marc Lipman, Anne O'Garra

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141 Citations (Scopus)


Rationale:New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations.Objectives:To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases.Methods:We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations.Measurements and Main Results:An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls.Conclusions:Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

Original languageEnglish
Article numbere70630
JournalPLoS One
Issue number8
Publication statusPublished - 5 Aug 2013
Externally publishedYes


ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Bloom, C. I., Graham, C. M., Berry, M. P. R., Rozakeas, F., Redford, P. S., Wang, Y., Xu, Z., Wilkinson, K. A., Wilkinson, R. J., Kendrick, Y., Devouassoux, G., Ferry, T., Miyara, M., Bouvry, D., Dominique, V., Gorochov, G., Blankenship, D., Saadatian, M., Vanhems, P., ... O'Garra, A. (2013). Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers. PLoS One, 8(8), [e70630].