TRANSLATE TB
Research type
Research Study
Full title
Evaluating the Risk of Progression in Latent Tuberculosis Infection using Gene Transcription Signatures
IRAS ID
295597
Contact name
Paul Collini
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Clinicaltrials.gov Identifier
STH21649, STH number
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Summary of Research
Tuberculosis (TB) remains an important global health problem with more than 10 million people diagnosed each year. Prevention of active TB disease involves identifying those with ‘dormant’ infection, called Latent TB Infection (LTBI), before it can 'reactivate' and treating them with 3-6 months of prophylactic antimicrobials. Immune memory tests called Interferon Gamma Release Assays (IGRAs) can identify individuals with LTBI but lack precision to predict the minority who will progress to active TB. As well as those who have had recent exposure to people with TB, patients with medical conditions that are treated with drugs that suppress their immune systems are routinely screened for LTBI in the UK as they are at increased risk of TB reactivation. LTBI chemoprophylaxis (CP) isn’t perfect. It does not offer 100% efficacy and potentially promotes antimicrobial resistance in the community. It also carries a significant risk of side effects or unwanted interactions with other medication, both more common in those being treated with immunosuppressive medication. Thus a better means of identifying those most in need of CP is needed. A promising approach to predict risk of active disease is through analysis of gene activation (transcription responses) in the peripheral blood of those with LTBI. To date, this approach has been studied in countries with populations that have a high burden TB. It is unclear if transcription signatures will have equivalent potential in patients within the UK.
In this study we will evaluate whether these gene signatures are detectable in UK based patients with LTBI and active TB. We will investigate how the signatures are affected by underlying inflammatory conditions, their immunosuppressive treatment, TB treatment and chemoprophylaxis.Summary of Results
: Accurately identifying people who have become infected with TB before they develop active TB disease is important as it allows for the use of antibiotics to prevent the TB disease. This state is called latent TB or and the treatment is called TB preventative therapy or TPT. Current tests for TB infection cannot accurately distinguish between cleared infection, infection that will become active and infection that is already active. TPT is only appropriate for the second group. The “Evaluating the Risk of Progression in Latent Tuberculosis Infection using Gene Transcription Signatures (TRANscriptional Signatures for LATEnt TB: TRANSLATE TB)” study aimed to evaluate whether immune system gene responses might improve the accuracy of latent TB testing in a UK setting. It looked at 7 previously discovered gene signatures described in people with TB infection in other parts of the world where TB is much more common. TRANSLATE is a proof of concept study and represents the first time that TB signatures have been evaluated in a UK-based population with latent TB infection.
TRANSLATE Participants were recruited over an 18-month period between June 2021 and November 2022. In total, 94 participants were recruited to the study. 93 were approached: 2 failed approach-screening, and 91 gave consent and were enrolled. Ten did not meet the full screening criteria. Consequently, 81 participants had at least a baseline PAXgene® wholeblood sample taken for RNA extraction (gene response testing). Six participants were subsequently excluded from analysis resulting in a final total of 78 participants.
None of the gene responses investigated were statistically significantly different for participants with latent TB compared with healthy controls without latent TB. One group of gene responses (evaluated using the the Sweeney3 score) showed a large enough difference in those with latent TB that might be confirmed to be significant if compared using a larger number of participants. TRANSLATE was able to detect many of the same gene response signatures as seen in other studies from parts of the world where TB is very common. Future work with the TRANSLATE data may involve evaluating the best combinations of the genes tested within the study to create a new signature that might better identify patients with latent TB.REC name
East of Scotland Research Ethics Service REC 1
REC reference
21/ES/0050
Date of REC Opinion
18 May 2021
REC opinion
Further Information Favourable Opinion