Blood signature could improve early TB diagnosis

A gene signature in the bloodstream could reveal whether someone is going to develop active tuberculosis (TB) disease months before symptoms begin, research has shown.

The signature has been developed by a team led by the Francis Crick Institute and the University of Leicester, in collaboration with BIOASTER and bioMérieux in France and the University of Cape Town in South Africa

The research, published in Nature Communications, looked at 53 TB patients in Leicester 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.

This is the first study to link the presence of signature and the onset of early TB before the patient has symptoms. This small proof-of-principle study shows a promising new direction for TB detection and treatment, also with the prospect of intervening before individuals pose a risk of transmitting the infection to others.

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. Previous approaches to find the key genes used algorithms to highlight the genes whose activity changed the most during active TB. However, some of the genes that are most active during TB are also active in other infections such as viral infections.

“Being able to track TB patients’ contacts and take monthly blood samples gave us a unique insight into how immune responses develop,” explains Dr Pranab Haldar, Senior Clinical Lecturer in respiratory medicine at the University of Leicester. “There was a wide variation in the immune response between people, highlighting the limitations of taking a ‘one size fits all’ approach. The next step will be to better understand what the different responses mean and we will need to study larger groups in detail to achieve this."