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

Chloë I. Bloom(National Institute for Medical Research), Christine M. Graham(Centre National de la Recherche Scientifique), Matthew Berry(Imperial College Healthcare NHS Trust), Fotini Rozakeas(Centre National de la Recherche Scientifique), Paul S. Redford(Centre National de la Recherche Scientifique), Yuanyuan Wang, Zhaohui Xu, Katalin A. Wilkinson(University of Cape Town), Robert J. Wilkinson(University of Cape Town), Yvonne Kendrick(University of Oxford), Gilles Devouassoux(Hôpital de la Croix-Rousse), Tristan Ferry(Hôpital de la Croix-Rousse), Makoto Miyara(Inserm), Diane Bouvry(Hôpital Avicenne), Valeyre Dominique(Hôpital Avicenne), Guy Gorochov(Sorbonne Université), Derek Blankenship(Baylor Scott & White Health), Mitra Saadatian(Université Claude Bernard Lyon 1), P. Vanhems(Université Claude Bernard Lyon 1), Huw Beynon(Royal Free London NHS Foundation Trust), Rama Vancheeswaran(Barnet and Chase Farm NHS Hospitals Trust), Melissa Wickremasinghe(Imperial College Healthcare NHS Trust), Damien Chaussabel(Benaroya Research Institute), Jacques Banchereau, Virginia Pascual, Ling‐Pei Ho(Churchill Hospital), Marc Lipman(Royal Free London NHS Foundation Trust), Anne O’Garra(Imperial College London)
PLoS ONE
August 5, 2013
10.1371/journal.pone.0070630
Cited by 323Open Access
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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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