Posted by 
A gene signature in the bloodstream could reveal the risk of active tuberculosis (TB) disease before symptoms begin. Such a signature has now been developed by a team led by the Francis Crick Institute and University of Leicester, in collaboration with BIOASTER and bioMerieux in France and the University of Cape Town in South Africa.
The research, looked at 53 TB patients in Leicester, UK, and followed 108 of their close contacts over two years to see who developed active TB. They found that those who remained healthy showed no sustained gene signature, while six of the nine who went on to develop active TB showed a strong, sustained signature.
Two billion people worldwide have been estimated to have been infected by the bacterium that causes TB, but only 10% of them develop clinically active disease. Symptoms of active TB include persistent cough, weight loss, fever and breathing difficulties. TB can be fatal if left untreated, and even when treated promptly the symptoms can last for several weeks during which the patient remains infectious.
According to Professor Anne O’Garra, Group Leader at the Francis Crick Institute, treating active TB before symptoms start could spare patients from unpleasant symptoms, reduce the spread of disease and offer peace of mind to people who are not going to develop active TB. The next step will be to develop and test different gene signatures in larger groups of people, with the aim of being able to offer validated tests to patients.
The team previously identified the full blood gene signature for active TB, and various groups around the world have since reproduced this signature and tried to narrow it down to a handful of genes that could be used in a field test. The gene ‘signature’ refers to the genes that are either more or less active during active TB, representing the body’s response to the infection. Some of the genes that are most active during TB are also active in other infections such as viral infections.
In the latest study, the team first analysed blood samples from patients across London and Africa with latent and active TB. They used global gene signatures from these patients to develop, in collaboration with BIOASTER, a panel of 20 key genes, combining computational methods with their understanding of the immune response to exclude genes that signal a more general response to infection. They tested this alongside other gene sets in data from both TB patients and those with viral infections including flu.
The results showed that other gene signatures, developed by other groups using standard methods, inadvertently detected viral infection since they included more general immune response genes. However, this new study now shows that the new 20-gene signature did not detect viral infections. This 20-gene signature was then tested at the Crick in contacts of TB patients in Leicester, recruited by co-author Dr Pranab Haldar’s team at the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, a partnership between Leicester’s Hospitals and the University of Leicester. The signature was not sustained in contacts who remained healthy, while six of the nine who went on to develop active TB showed a strong, sustained signature.
haleplushearty.org