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

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

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
Volume8
Issue number8
DOIs
Publication statusPublished - 5 Aug 2013
Externally publishedYes

Fingerprint

Pulmonary Sarcoidosis
lung neoplasms
Pulmonary Tuberculosis
tuberculosis
pneumonia
Lung Neoplasms
Pneumonia
Pulmonary diseases
Sarcoidosis
Tuberculosis
Blood
lungs
blood
Lung Diseases
respiratory tract diseases
Interferons
Genes
interferons
Biomarkers
Glucocorticoids

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., ... O'Garra, A. (2013). Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers. PLoS One, 8(8), [e70630]. https://doi.org/10.1371/journal.pone.0070630

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

In: PLoS One, Vol. 8, No. 8, e70630, 05.08.2013.

Research output: Contribution to journalArticle

Bloom, CI, Graham, CM, Berry, MPR, Rozakeas, F, Redford, PS, Wang, Y, Xu, Z, Wilkinson, KA, Wilkinson, RJ, Kendrick, Y, Devouassoux, G, Ferry, T, Miyara, M, Bouvry, D, Dominique, V, Gorochov, G, Blankenship, D, Saadatian, M, Vanhems, P, Beynon, H, Vancheeswaran, R, Wickremasinghe, M, Chaussabel, DJ, Banchereau, J, Pascual, V, Ho, LP, Lipman, M & O'Garra, A 2013, 'Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers', PLoS One, vol. 8, no. 8, e70630. https://doi.org/10.1371/journal.pone.0070630
Bloom, Chloe I. ; Graham, Christine M. ; Berry, Matthew P R ; Rozakeas, Fotini ; Redford, Paul S. ; Wang, Yuanyuan ; Xu, Zhaohui ; Wilkinson, Katalin A. ; Wilkinson, Robert J. ; Kendrick, Yvonne ; Devouassoux, Gilles ; Ferry, Tristan ; Miyara, Makoto ; Bouvry, Diane ; Dominique, Valeyre ; Gorochov, Guy ; Blankenship, Derek ; Saadatian, Mitra ; Vanhems, Phillip ; Beynon, Huw ; Vancheeswaran, Rama ; Wickremasinghe, Melissa ; Chaussabel, Damien J. ; Banchereau, Jacques ; Pascual, Virginia ; Ho, Ling pei ; Lipman, Marc ; O'Garra, Anne. / Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers. In: PLoS One. 2013 ; Vol. 8, No. 8.
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abstract = "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.",
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AU - Bloom, Chloe I.

AU - Graham, Christine M.

AU - Berry, Matthew P R

AU - Rozakeas, Fotini

AU - Redford, Paul S.

AU - Wang, Yuanyuan

AU - Xu, Zhaohui

AU - Wilkinson, Katalin A.

AU - Wilkinson, Robert J.

AU - Kendrick, Yvonne

AU - Devouassoux, Gilles

AU - Ferry, Tristan

AU - Miyara, Makoto

AU - Bouvry, Diane

AU - Dominique, Valeyre

AU - Gorochov, Guy

AU - Blankenship, Derek

AU - Saadatian, Mitra

AU - Vanhems, Phillip

AU - Beynon, Huw

AU - Vancheeswaran, Rama

AU - Wickremasinghe, Melissa

AU - Chaussabel, Damien J.

AU - Banchereau, Jacques

AU - Pascual, Virginia

AU - Ho, Ling pei

AU - Lipman, Marc

AU - O'Garra, Anne

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N2 - 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.

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