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

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dc.contributor.authorBloom, Chloe Ien_ZA
dc.contributor.authorGraham, Christine Men_ZA
dc.contributor.authorBerry, Matthew P Ren_ZA
dc.contributor.authorRozakeas, Fotinien_ZA
dc.contributor.authorRedford, Paul Sen_ZA
dc.contributor.authorWang, Yuanyuanen_ZA
dc.contributor.authorXu, Zhaohuien_ZA
dc.contributor.authorWilkinson, Katalin Aen_ZA
dc.contributor.authorWilkinson, Robert Jen_ZA
dc.contributor.authorKendrick, Yvonneen_ZA
dc.date.accessioned2015-12-28T06:47:36Z
dc.date.available2015-12-28T06:47:36Z
dc.date.issued2013en_ZA
dc.description.abstractRationale: 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.en_ZA
dc.identifier.apacitationBloom, C. I., Graham, C. M., Berry, M. P. R., Rozakeas, F., Redford, P. S., Wang, Y., ... Kendrick, Y. (2013). Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers. <i>PLoS One</i>, http://hdl.handle.net/11427/16037en_ZA
dc.identifier.chicagocitationBloom, Chloe I, Christine M Graham, Matthew P R Berry, Fotini Rozakeas, Paul S Redford, Yuanyuan Wang, Zhaohui Xu, Katalin A Wilkinson, Robert J Wilkinson, and Yvonne Kendrick "Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/16037en_ZA
dc.identifier.citationBloom, C. I., Graham, C. M., Berry, M. P., Rozakeas, F., Redford, P. S., Wang, Y., ... & Devouassoux, G. (2013). Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers. PloS one, 8(8), e70630. doi:10.1371/journal.pone.0070630en_ZA
dc.identifier.ris TY - Journal Article 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 AB - 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. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0070630 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers TI - Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers UR - http://hdl.handle.net/11427/16037 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16037
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0070630
dc.identifier.vancouvercitationBloom CI, Graham CM, Berry MPR, Rozakeas F, Redford PS, Wang Y, et al. Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers. PLoS One. 2013; http://hdl.handle.net/11427/16037.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2013 Bloom et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherSarcoidosisen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherPneumoniaen_ZA
dc.subject.otherBlooden_ZA
dc.subject.otherLung and intrathoracic tumorsen_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherInflammatory diseasesen_ZA
dc.subject.otherSupport vector machinesen_ZA
dc.titleTranscriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancersen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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