Characterising Phenotypes of Mtb Infection (ISIT-TB)

• Research type

  Research Study

• Full title

  A Novel Whole Blood Transcriptomic Signature to Characterise Phenotypes of Mycobacterium Tuberculosis Infection (ISIT-TB)

• IRAS ID

  165646

• Contact name

  Pranabashis Haldar

• Contact email

  ph62@le.ac.uk

• Sponsor organisation

  University of Leicester

• Duration of Study in the UK

  4 years, 0 months, 0 days

• Research summary

  Research Summary

  Tuberculosis (TB) is a disease caused by bacteria called Mycobacterium tuberculosis (M. tuberculosis). TB usually affects the lungs, but it can also affect other parts of the body. TB infection is increasing in the UK. It can result in serious illness and remains a major cause of death in the world. However, not everyone infected with M. tuberculosis becomes sick and exhibits features of active TB disease. Thus, there are two TB-related conditions:

  •Active TB disease and
  •Latent TB infection (LTBI)

  Those with LTBI do not feel sick and do not have any symptoms - they are infected but not clinically affected. Currently, the diagnosis of LTBI is based solely on evidence of immune reaction, classically by a positive reaction to the Tuberculin Skin Test or a positive blood test (QuantiFERON-TB Gold In-Tube). Overall, without treatment, about 10-20% of LTBI patients will develop active TB disease at some point in their lives, with most developing TB disease in the first two years of infection.
  Clinically, there is a gap in our diagnostic tool kit for LTBI. The current tests lack diagnostic accuracy, can be misused and we do not fully understand their variability. Additionally, there is no current test that can:

  •differentiate active TB disease from LTBI or
  •identify those with LTBI who may progress to active TB disease

  Identification of those LTBI individuals most at risk of developing active TB disease would help clinicians to target preventative therapy. This is an important issue as disease treatment is lengthy with potentially toxic drugs.

  To improve the detection and treatment of LTBI, we need a better understanding of how the immune system responds to it. This study aims to identify the patterns of gene activity that represent the immune response of patients with active TB disease and LTBI.

  Summary of Results

  Tuberculosis is s bacterial infection that can exist either in a dormant form within the body (latent TB infection) or cause active disease (TB). This study set out to develop new blood tests for TB by measuring immune responses to the infection in its active and latent forms. We performed RNA sequencing of blood which measures the expression of genes within white blood cells, which are important for fighting infections. In this way we could find out about the different immune responses that occur in study participants that had latent TB and active TB. By taking blood at different timepoints over two years, we could also measure the change in different immune responses over time within subgroups that either went on to develop active TB from a latent state, or who were treated for the disease and returned to normal health. This allowed us to identify unique patterns of gene expression that: i. were associated with having active TB, and could be developed into a diagnostic tool; ii. associated with future risk of developing TB in someone with latent infection and could be developed into a tool to predict risk of disease; and iii. associated with a favourable response to treatment in people given treatment for disease, and could be developed into a biomarker of treatment response.
  These immune signatures are now being utilised in development of new medical devices to be trialled in clinical settings to determine how they can help us improve management of this devastating disease.

• REC name

  East Midlands - Nottingham 1 Research Ethics Committee

• REC reference

  15/EM/0109

• Date of REC Opinion

  6 May 2015

• REC opinion

  Further Information Favourable Opinion