Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.
BACKGROUND
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.


OBJECTIVE
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.


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.
Division of Immunoregulation, MRC National Institute for Medical Research, London, United Kingdom. cbloom@nimr.mrc.ac.uk
Chloe I
CI
Bloom
Christine M
CM
Graham
Matthew P R
MP
Berry
Fotini
F
Rozakeas
Paul S
PS
Redford
Yuanyuan
Y
Wang
Zhaohui
Z
Xu
Katalin A
KA
Wilkinson
Robert J
RJ
Wilkinson
Yvonne
Y
Kendrick
Gilles
G
Devouassoux
Tristan
T
Ferry
Makoto
M
Miyara
Diane
D
Bouvry
Dominique
D
Valeyre
Valeyre
V
Dominique
Guy
G
Gorochov
Derek
D
Blankenship
Mitra
M
Saadatian
Phillip
P
Vanhems
Huw
H
Beynon
Rama
R
Vancheeswaran
Melissa
M
Wickremasinghe
Damien
D
Chaussabel
Jacques
J
Banchereau
Virginia
V
Pascual
Ling-Pei
LP
Ho
Marc
M
Lipman
Anne
A
O'Garra
D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007372:Interferons / Q000502:physiology; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis; D009504:Neutrophils / Q000378:metabolism; D011014:Pneumonia / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism; D017565:Sarcoidosis, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D014158:Transcription, Genetic; D059467:Transcriptome; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy
D000995:Antitubercular Agents; D015415:Biomarkers; D005938:Glucocorticoids; D018836:Inflammation Mediators; D051192:Receptors, Pattern Recognition; D007372:Interferons