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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Detectable Changes in The Blood Transcriptome Are Present after Two Weeks of Antituberculosis Therapy
PLoS ONE, Volume 7, No. 10, Article e46191, Year 2012
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Description
Rationale: Globally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually
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Effective antituberculosis treatment monitoring is difficult as there are no existing biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance. Objectives: To determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response. Methods: Blood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis. Results: An active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient. Conclusions: Significant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response. © 2012 Bloom et al.
Authors & Co-Authors
Bloom, Chloe I.
United Kingdom, London
Mrc National Institute for Medical Research
Graham, Christine Marian
United Kingdom, London
Mrc National Institute for Medical Research
Berry, Matthew P.R.
United Kingdom, London
Mrc National Institute for Medical Research
United Kingdom, London
Imperial College Healthcare Nhs Trust
Andrea Wilkinson, Katalin Andrea
United Kingdom, London
Mrc National Institute for Medical Research
South Africa, Cape Town
University of Cape Town
Oni, Tolu
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
Rozakeas, Fotini
United Kingdom, London
Mrc National Institute for Medical Research
Xu, Zhaohui
United States, Dallas
Baylor Institute for Immunology Research
Rossello-Urgell, Jose
United States, Dallas
Baylor Institute for Immunology Research
Chaussabel, Damien
United States, Dallas
Baylor Institute for Immunology Research
United States, Seattle
Benaroya Research Institute at Virginia Mason
Banchereau, Jacques F.J.
United States, Dallas
Baylor Institute for Immunology Research
Pascual, Virginia
United States, Dallas
Baylor Institute for Immunology Research
Lipman, Marc CI
United Kingdom, London
The Royal Free Hospital
Wilkinson, Robert J.
United Kingdom, London
Mrc National Institute for Medical Research
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
O’Garra, Anne
United Kingdom, London
Mrc National Institute for Medical Research
Statistics
Citations: 195
Authors: 14
Affiliations: 7
Identifiers
Doi:
10.1371/journal.pone.0046191
e-ISSN:
19326203
Research Areas
Health System And Policy
Study Design
Cohort Study
Study Approach
Quantitative
Study Locations
South Africa