domingo, 29 de agosto de 2010

PHG Foundation | Genetic transcriptional signature to predict active TB



Genetic transcriptional signature to predict active TB
24 August 2010 | By Dr Susmita Chowdhury | Research article


Tuberculosis (TB) is a common, often deadly infectious disease usually affecting the lungs. Approximately two million people, mostly from the developing world, died from this disease in 2008 (according to WHO). A third of the world’s population are thought to be infected with the causative bacterium, Mycobacterium tuberculosis. However, only one in ten of these carriers will develop fully blown TB over their lifetime. Current tests cannot identify which individuals will develop the disease and this means that anti-TB drugs could potentially be given to everyone who is shown to be infected with the bacterium. A study [Berry et al. (2010) Nature 19 August doi: 10.1038/nature09247] recently published in Nature reports on a relatively new and complex genomic test to investigate biological markers that have the potential for diagnosing and predicting active TB.

The researchers used a technique called ‘genomic transcription profiling’ that assesses gene activity by measuring the types and quantities of RNA cells produce. They compared the transcriptional profiles of expressed genes in blood samples from three different groups of subjects: those with active TB before treatment, those with latent TB (i.e. apparently healthy but infected carriers) and healthy controls. The aim was to identify a gene transcript pattern that was similar in people with active TB and “high risk” latent patients.

A distinctive ‘393 transcript signature’ was identified in patients with active TB, and validated in two independent cohorts from the UK and South Africa, with further testing in people with other diseases including bacterial infections. The 393-transcript signature was found to be characteristic of active TB, and returned to normal after treatment. The researchers found that 10-25% of the patients with latent TB also displayed this characteristic ‘active’ or high risk profile. The paper found that the test had a sensitivity of 62% and a specificity of 92% - that is, it would identify 38% of patients as not having active TB when they do, and detect 8% of those without TB as having the disease.

Comment: This study reports on a transcriptional signature of TB from human blood that may have important implications for better diagnosis, treatment and prevention. It may help to identify patients with active TB and thus reduce the indiscriminate use of TB medication. However, the test’s accuracy in predicting which TB patients develop the active disease needs to be measured in the general population in a prospective study having been developed and initially tested in a highly selected group
PHG Foundation | Genetic transcriptional signature to predict active TB

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