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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers
PLoS ONE, Volume 8, No. 8, Article e70630, Year 2013
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Description
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. © 2013 Bloom et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s001.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s002.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s003.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s004.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s005.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s006.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s007.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s008.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s009.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s010.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s011.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s012.pptx
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s013.pptx
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s014.pptx
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s015.pptx
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s016.pptx
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s017.pptx
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s018.pptx
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s019.pptx
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s020.pptx
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s021.pptx
https://efashare.b-cdn.net/share/pmc/articles/PMC3734176/bin/pone.0070630.s022.pptx
Authors & Co-Authors
Bloom, Chloe I.
United Kingdom, London
Mrc National Institute for Medical Research
Graham, Christine Marian
United Kingdom, London
Mrc National Institute for Medical Research
Berry, Matthew P.R.
United Kingdom, London
Mrc National Institute for Medical Research
United Kingdom, London
Imperial College Healthcare Nhs Trust
Rozakeas, Fotini
United Kingdom, London
Mrc National Institute for Medical Research
Redford, Paul S.
United Kingdom, London
Mrc National Institute for Medical Research
Wang, Yuanyuan
United States, Dallas
Baylor Institute for Immunology Research
Xu, Zhaohui
United States, Dallas
Baylor Institute for Immunology Research
Andrea Wilkinson, Katalin Andrea
United Kingdom, London
Mrc National Institute for Medical Research
South Africa, Cape Town
University of Cape Town
Wilkinson, Robert J.
United Kingdom, London
Mrc National Institute for Medical Research
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
Kendrick, Yvonne
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
Devouassoux, Gilles
France, Lyon
Hopital de la Croix-rousse
Ferry, Tristan
France, Lyon
Hopital de la Croix-rousse
Miyara, Makoto
France, Paris
Inserm
Bouvry, Diane
France, Bobigny
Hopital Avicenne
Dominique, Valeyre
France, Bobigny
Hopital Avicenne
Gorochov, Guy
France, Paris
Laboratoire Cnrs Laboratoire D'immunologie Cellulaire et Tissulaire
Blankenship, Derek
United States
Baylor Health Care System
Saadatian, Mohammad
France, Lyon
Université de Lyon
Vanhems, Philippe V.
France, Lyon
Hopital Edouard Herriot
France, Villeurbanne
Laboratoire de Biométrie et Biologie Évolutive
Beynon, Huw
United Kingdom, London
Royal Free London Nhs Foundation Trust
Vancheeswaran, Rama
United Kingdom, London
Royal Free London Nhs Foundation Trust
Wickremasinghe, Melissa
United Kingdom, London
Imperial College Healthcare Nhs Trust
Chaussabel, Damien
United States, Dallas
Baylor Institute for Immunology Research
United States, Seattle
Benaroya Research Institute at Virginia Mason
Banchereau, Jacques F.J.
United States, Dallas
Baylor Institute for Immunology Research
Pascual, Virginia
United States, Dallas
Baylor Institute for Immunology Research
Ho, Ling Pei
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
United Kingdom, Oxford
Churchill Hospital
Lipman, Marc CI
United Kingdom, London
Royal Free London Nhs Foundation Trust
United Kingdom, London
University College London
O’Garra, Anne
United Kingdom, London
Mrc National Institute for Medical Research
United Kingdom, London
Imperial College London
Statistics
Citations: 253
Authors: 28
Affiliations: 18
Identifiers
Doi:
10.1371/journal.pone.0070630
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics