title: The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis.
abstract: BACKGROUND
  Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis.
  
  
  METHODS
  A novel cohort of patients with extra-pulmonary TB and sarcoidosis was recruited and the transcriptional response of these patients compared to those with pulmonary TB using a variety of transcriptomic approaches including testing a previously defined 380 gene meta-signature of active TB.
  
  
  RESULTS
  The 380 meta-signature broadly differentiated active TB from healthy controls in this new dataset consisting of pulmonary and extra-pulmonary TB. The top 15 genes from this meta-signature had a lower sensitivity for differentiating extra-pulmonary TB from healthy controls as compared to pulmonary TB. We found the blood transcriptional responses in pulmonary and extra-pulmonary TB to be heterogeneous and to reflect the extent of symptoms of disease.
  
  
  CONCLUSIONS
  The transcriptional signature in extra-pulmonary TB demonstrated heterogeneity of gene expression reflective of symptom status, while the signature of pulmonary TB was distinct, based on a higher proportion of symptomatic individuals. These findings are of importance for the rational design and implementation of mRNA based TB diagnostics.
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Blankley
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Graham
authors.affiliation: Baylor Research Institute, Baylor Scott & White, Dallas, Texas, United States of America.
authors.forename: Jacob
authors.initials: J
authors.lastname: Turner
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.|Department of Respiratory Medicine, Imperial College Healthcare NHS Trust, St Mary's Hospital, London, United Kingdom.
authors.forename: Matthew P R
authors.initials: MP
authors.lastname: Berry
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Chloe I
authors.initials: CI
authors.lastname: Bloom
authors.affiliation: Baylor Institute for Immunology Research/ANRS Center for Human Vaccines, INSERM, Dallas, Texas, United States of America.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Baylor Institute for Immunology Research/ANRS Center for Human Vaccines, INSERM, Dallas, Texas, United States of America.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, 06032, Connecticut, United States of America.
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.affiliation: Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
authors.affiliation: Department of Respiratory Medicine, King's College London, London, United Kingdom.
authors.forename: Ronan
authors.initials: R
authors.lastname: Breen
authors.affiliation: Department of Respiratory Medicine, King's College London, London, United Kingdom.|Division of Asthma, Allergy and Lung Biology, King's College London, London, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Santis
authors.affiliation: Baylor Research Institute, Baylor Scott & White, Dallas, Texas, United States of America.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Blankenship
authors.affiliation: Department of Respiratory Medicine, Royal Free London NHS Foundation Trust, London, United Kingdom.|Division of Medicine, University College London, London, United Kingdom.
authors.forename: Marc
authors.initials: M
authors.lastname: Lipman
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.|Department of Medicine, NHLI, Imperial College, London, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: O'Garra
mesh_terms: D001772:Blood Cell Count; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D012507:Sarcoidosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D014376:Tuberculosis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation