Gene-expression patterns in whole blood identify subjects at risk for recurrent tuberculosis.
BACKGROUND
The majority of patients with tuberculosis who comply with appropriate treatment are cured. However, approximately 5% subsequently have a repeat disease episode, usually within 2 years of successful combination therapy. Presently, there is no way of predicting which patients will experience a relapse.


METHODS
We identified 10 subjects who had previously experienced recurrent tuberculosis and carefully matched them to cured subjects who had had only 1 episode of tuberculosis, to patients with active tuberculosis, and to latently infected healthy subjects. We compared their ex vivo whole-blood gene-expression profiles by use of DNA array technology and confirmed the results by use of quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).


RESULTS
The 4 clinical tuberculosis groups exhibited distinct patterns of gene expression. The gene-transcript profiles of the patients with recurrent tuberculosis were more similar to those of the patients with active tuberculosis than to those of the cured or latently infected subjects. Discriminant analysis of a training data set showed that 9 genes were sufficient to classify the subjects. We confirmed that measurement of the expression of these genes by qRT-PCR can accurately discriminate between subjects in a test set of samples.


CONCLUSIONS
A simple test based on gene-expression patterns may be used as a biomarker of cure while identifying patients who are at risk for relapse. This would facilitate the introduction of new tuberculosis drugs.
Mistry
Rohit
R
GlaxoSmithKline, Stevenage, UK.
Cliff
Jacqueline M
JM
Clayton
Christopher L
CL
Beyers
Nulda
N
Mohamed
Yasmin S
YS
Wilson
Paul A
PA
Dockrell
Hazel M
HM
Wallace
Don M
DM
van Helden
Paul D
PD
Duncan
Ken
K
Lukey
Pauline T
PT
D015415:Biomarkers / Q000097:blood; D001773:Blood Cells / Q000378:metabolism*; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012008:Recurrence; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D014376:Tuberculosis / Q000097:blood* / Q000175:diagnosis
D015415:Biomarkers; D011506:Proteins; D012333:RNA, Messenger; C473085:SOCS6 protein, human; D050826:Suppressor of Cytokine Signaling Proteins