Genetic link to Tuberculosis prognosis

Researchers have come one step closer to being able to predict who will develop full-blown symptoms following infection with the tuberculosis (TB) bacterium.

An international study, published in Nature, has identified a blood 'signature' that can distinguish those who have 'active' TB from those carrying a latent (asymptomatic) form of the bacterium. Researchers hope to use this signature to identify TB carriers who are likely to develop the disease before they become symptomatic, potentially saving many lives.

TB is an infectious bacterial disease which devastates the lungs, causing two million deaths per year worldwide. However, only a small number of people infected with the TB bacterium go on to develop the disease and it is currently impossible to distinguish these people from those who carry the infection but will remain healthy.

Lead researcher Dr Anne O'Garra, from the National Institute for Medical Research in London, said: 'What most intrigued me was that approximately a third of the world has been exposed or infected with the TB bacterium but only ten per cent of these people get sick and the question is why - what determines when people get active tuberculosis?'

The study - conducted in the UK and South Africa - identified a gene profile or 'signature' consisting of 393 genes that have altered activity in the blood cells of people infected with TB compared to healthy individuals. The researchers found they could correctly classify each person as having an active infection, a latent infection or no infection based solely on their gene activity signature.

Ten per cent of individuals with a latent TB infection had signatures similar to those with an active infection, suggesting these may be the ten per cent that go on to develop the full disease. The researchers now plan to follow these patients to see if this is the case.

Dr Marc Lipman from the British Thoracic Society, who was not part of the study, said 'This for the first time perhaps enables us to start to design tests which can predict who is at highest risk of progressing to active disease and also how we might stop that occurring in the first place'.

Study co-author Mr Matthew Berry added: 'What such a test would enable is very targeted treatment. Instead of trying to treat everyone with latent TB you could focus all of your efforts on that ten per cent who would develop the disease'.

However, much more work needs to be done and Dr Lipman believes that 'any such advance is 20-30 years away'.

'We just have to prove it now, but it's very promising', added Dr O'Garra.