RT Journal Article
SR Electronic
T1 A change in blood transcriptional signatures accompanies successful tuberculosis therapy
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P2640
VO 40
IS Suppl 56
A1 Chloe Bloom
A1 Christine Graham
A1 Matthew Berry
A1 Katalin Wilkinson
A1 Oni Tolu
A1 Fotini Rozakeas
A1 Zhaohui Xu
A1 Jose Rossello-Urgell
A1 Damien Chaussabel
A1 Jacques Banchereau
A1 Virginia Pascual
A1 Marc Lipman
A1 Robert Wilkinson
A1 Anne O'Garra
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P2640.abstract
AB IntroductionInadequate treatment of patients with active TB leads to worsening disease, infection transmission and drug resistance. Effective anti-TB therapy monitoring is difficult as the best accepted method is the 2-month sputum culture conversion. However this has low sensitivity for predicting an individuals response, and difficult to implement since culture results are not available in 30-50% of patients. No recognised biomarkers of treatment response earlier than 2 months exist.AimsDetermine if blood transcriptional profiles can be used in early TB treatment monitoring.MethodsMtb culture-positive, HIV-uninfected, pulmonary TB patients were recruited in Cape Town, South Africa and London. Patients with latent TB infection were also recruited. Whole blood samples were taken before, during, and after, 6 months of standard first line TB drug therapy. Samples were processed for microarray analysis (Illumina). Changes in transcriptional expression were analysed. An algorithm to quantify the changes was also devised.ResultsAll patients responded successfully to therapy. An active TB transcriptional signature was derived by comparing the untreated active and latent TB patients. A specific treatment response transcriptional signature was derived comparing patients before and after treatment. Both signatures showed significant changes in response to treatment and could be quantified for individual patients.ConclusionThese results provide evidence that blood transcriptional signatures could be used as biomarkers of a successful treatment response. These potential biomarkers, measured in whole blood, could assess treatment response in patients more consistently than currently available tests.