Blood Transcriptional Profiles in Active and Latent Tuberculosis UK (Training Set)

The aim of the project was to define transcriptional signatures in whole blood of TB patients (before drug treatment) and healthy controls to distinguish the signature of Latent and Active TB patients from each other and from healthy controls. This will help in diagnosis of active tuberculosis which normally relies on culture of the bacilli, which can take up to 6 wks, and sometimes the bacilli cannot be obtained from sputum thus requiring invasive techniques obtaining bronchoalveolar lavage (BAL). In some cases the bacill cannot be grown from sputum or BAL. Secondly the aim was to determine whether Latent patients have a homogeneous or heterogeneous signature, one may expect the latter since it is not possible to determine by the present tests (Tuberculin skin test - TST - or MTb antigen responsiveness of blood cells to produce IFN-gamma - IGRA assay) whether the mycobacteria has been cleared, is still present but is controlled, or if patients are recently infected or reactivated and will develop active TB. The latter situation may be determined if Latent patients have a blood transcriptional signature similar to that in Active patients. The transcriptional signature in Active TB patients may also provide information as to the factors leading to immunopathogenesis, thus possibly identifying therapeutic targets. The transcriptional profile in Latent TB may give information as to the protective factors controlling the infection, thus important for monitoring vaccine development. A further aim was to examine the transcriptional blood profile of active TB patients at the time of recruitment (before drug treatment) and then subsequently at specific time points after drug treatment to determine whether the signature is extingsuihed with treatment and when. London is a site of intermediate burden of TB - the study was initiated in London, across a broad range of ethnicities to obtain a robust signature that could be used in different developing countries where there is a high burden TB disease.

42

Berry MP, Graham CM, McNab FW, Xu Z, Bloch SA, Oni T, Wilkinson KA, Banchereau R, Skinner J, Wilkinson RJ, Quinn C, Blankenship D, Dhawan R, Cush JJ, Mejias A, Ramilo O, Kon OM, Pascual V, Banchereau J, Chaussabel D, O'Garra A