• 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, Dominique Valeyre, Valeyre Dominique, Guy Gorochov, Derek Blankenship, Mitra Saadatian, Phillip Vanhems, Huw Beynon, Rama Vancheeswaran, Melissa Wickremasinghe, Damien Chaussabel, Jacques Banchereau, Virginia Pascual, Ling-Pei Ho, Marc Lipman, and Anne O'Garra.
• Division of Immunoregulation, MRC National Institute for Medical Research, London, United Kingdom. cbloom@nimr.mrc.ac.uk
• Plos One. 2013 Jan 1; 8 (8): e70630.

RationaleNew 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.ObjectivesTo 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.MethodsWe 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 ResultsAn 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.ConclusionsTuberculosis 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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