The transcriptional signature of active tuberculosis reflects symptom status in extra-pulmonary and pulmonary tuberculosis

Simon Blankley, Christine M. Graham, Jacob Turner, Matthew P.R. Berry, Chloe I. Bloom, Zhaohui Xu, Virginia Pascual, Jacques Banchereau, Damien J. Chaussabel, Ronan Breen, George Santis, Derek M. Blankenship, Marc Lipman, Anne O'Garra

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis. Methods: A novel cohort of patients with extra-pulmonary TB and sarcoidosis was recruited and the transcriptional response of these patients compared to those with pulmonary TB using a variety of transcriptomic approaches including testing a previously defined 380 gene metasignature of active TB. Results: The 380 meta-signature broadly differentiated active TB from healthy controls in this new dataset consisting of pulmonary and extra-pulmonary TB. The top 15 genes from this metasignature had a lower sensitivity for differentiating extra-pulmonary TB from healthy controls as compared to pulmonary TB. We found the blood transcriptional responses in pulmonary and extra-pulmonary TB to be heterogeneous and to reflect the extent of symptoms of disease. Conclusions: The transcriptional signature in extra-pulmonary TB demonstrated heterogeneity of gene expression reflective of symptom status, while the signature of pulmonary TB was distinct, based on a higher proportion of symptomatic individuals. These findings are of importance for the rational design and implementation of mRNA based TB diagnostics.

Original languageEnglish
Article numbere0162220
JournalPLoS One
Volume11
Issue number10
DOIs
Publication statusPublished - 1 Oct 2016
Externally publishedYes

Fingerprint

Pulmonary Tuberculosis
tuberculosis
Gene expression
signs and symptoms (animals and humans)
Tuberculosis
lungs
Lung
Blood
Genes
Biomarkers
Microarrays
Pulmonary Sarcoidosis
Messenger RNA
Testing
gene expression
Gene Expression
Mycobacterium Infections
Transcriptome
Mycobacterium tuberculosis
Cause of Death

ASJC Scopus subject areas

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

Cite this

Blankley, S., Graham, C. M., Turner, J., Berry, M. P. R., Bloom, C. I., Xu, Z., ... O'Garra, A. (2016). The transcriptional signature of active tuberculosis reflects symptom status in extra-pulmonary and pulmonary tuberculosis. PLoS One, 11(10), [e0162220]. https://doi.org/10.1371/journal.pone.0162220

The transcriptional signature of active tuberculosis reflects symptom status in extra-pulmonary and pulmonary tuberculosis. / Blankley, Simon; Graham, Christine M.; Turner, Jacob; Berry, Matthew P.R.; Bloom, Chloe I.; Xu, Zhaohui; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien J.; Breen, Ronan; Santis, George; Blankenship, Derek M.; Lipman, Marc; O'Garra, Anne.

In: PLoS One, Vol. 11, No. 10, e0162220, 01.10.2016.

Research output: Contribution to journalArticle

Blankley, S, Graham, CM, Turner, J, Berry, MPR, Bloom, CI, Xu, Z, Pascual, V, Banchereau, J, Chaussabel, DJ, Breen, R, Santis, G, Blankenship, DM, Lipman, M & O'Garra, A 2016, 'The transcriptional signature of active tuberculosis reflects symptom status in extra-pulmonary and pulmonary tuberculosis', PLoS One, vol. 11, no. 10, e0162220. https://doi.org/10.1371/journal.pone.0162220
Blankley, Simon ; Graham, Christine M. ; Turner, Jacob ; Berry, Matthew P.R. ; Bloom, Chloe I. ; Xu, Zhaohui ; Pascual, Virginia ; Banchereau, Jacques ; Chaussabel, Damien J. ; Breen, Ronan ; Santis, George ; Blankenship, Derek M. ; Lipman, Marc ; O'Garra, Anne. / The transcriptional signature of active tuberculosis reflects symptom status in extra-pulmonary and pulmonary tuberculosis. In: PLoS One. 2016 ; Vol. 11, No. 10.
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