Host blood RNA signatures predict the outcome of tuberculosis treatment

Ethan G Thompson; Ying Du; Stephanus T Malherbe; Smitha Shankar; Jackie Braun; Joe Valvo; Katharina Ronacher; Gerard Tromp; David L Tabb; David Alland; Shubhada Shenai; Laura E Via; James Warwick; Alan Aderem; Thomas J Scriba; Jill Winter; Gerhard Walzl; Daniel E Zak; Nelita Du Plessis; Andre G Loxton; Novel N Chegou; Myungsun Lee; the Catalysis TB–Biomarker Consortium

doi:10.1016/j.tube.2017.08.004

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Host blood RNA signatures predict the outcome of tuberculosis treatment

Journal article

Open access

Peer reviewed

Host blood RNA signatures predict the outcome of tuberculosis treatment

Ethan G Thompson, Ying Du, Stephanus T Malherbe, Smitha Shankar, Jackie Braun, Joe Valvo, Katharina Ronacher, Gerard Tromp, David L Tabb, David Alland, …

Tuberculosis (Edinburgh, Scotland), Vol.107, pp.48-58

12/2017

DOI: https://doi.org/10.1016/j.tube.2017.08.004

PMCID: PMC5658513

PMID: 29050771

Abstract

Host response

Biomarkers

Mitochondria

Tuberculosis treatment

Transcriptome

Biomarkers for tuberculosis treatment outcome will assist in guiding individualized treatment and evaluation of new therapies. To identify candidate biomarkers, RNA sequencing of whole blood from a well-characterized TB treatment cohort was performed. Application of a validated transcriptional correlate of risk for TB revealed symmetry in host gene expression during progression from latent TB infection to active TB disease and resolution of disease during treatment, including return to control levels after drug therapy. The symmetry was also seen in a TB disease signature, constructed from the TB treatment cohort, that also functioned as a strong correlate of risk. Both signatures identified patients at risk of treatment failure 1–4 weeks after start of therapy. Further mining of the transcriptomes revealed an association between treatment failure and suppressed expression of mitochondrial genes before treatment initiation, leading to development of a novel baseline (pre-treatment) signature of treatment failure. These novel host responses to TB treatment were integrated into a five-gene real-time PCR-based signature that captures the clinically relevant responses to TB treatment and provides a convenient platform for stratifying patients according to their risk of treatment failure. Furthermore, this 5-gene signature is shown to correlate with the pulmonary inflammatory state (as measured by PET-CT) and can complement sputum-based Gene Xpert for patient stratification, providing a rapid and accurate alternative to current methods.

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Title: Host blood RNA signatures predict the outcome of tuberculosis treatment
Creators: Ethan G Thompson - The Center for Infectious Disease Research, Seattle, WA, USA
Ying Du - The Center for Infectious Disease Research, Seattle, WA, USA
Stephanus T Malherbe - Department of Science and Technology, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
Smitha Shankar - The Center for Infectious Disease Research, Seattle, WA, USA
Jackie Braun - The Center for Infectious Disease Research, Seattle, WA, USA
Joe Valvo - The Center for Infectious Disease Research, Seattle, WA, USA
Katharina Ronacher - Department of Science and Technology, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
Gerard Tromp - Department of Science and Technology, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
David L Tabb - Department of Science and Technology, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
David Alland - Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Rutgers Biomedical & Health Sciences, Newark, NJ, USA
Shubhada Shenai - Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Rutgers Biomedical & Health Sciences, Newark, NJ, USA
Laura E Via - Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
James Warwick - Western Cape Academic Positron Emission Tomography–Computed Tomography Centre, Tygerberg Academic Hospital, Cape Town, South Africa
Alan Aderem - The Center for Infectious Disease Research, Seattle, WA, USA
Thomas J Scriba - South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Jill Winter - Catalysis Foundation for Health, Emeryville, CA, USA
Gerhard Walzl - Department of Science and Technology, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
Daniel E Zak - The Center for Infectious Disease Research, Seattle, WA, USA
Nelita Du Plessis - Department of Science and Technology, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
Andre G Loxton - Department of Science and Technology, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
Novel N Chegou - Department of Science and Technology, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
Myungsun Lee - International Tuberculosis Research Center, Seoul, South Korea
the Catalysis TB–Biomarker Consortium
Publication Details: Tuberculosis (Edinburgh, Scotland), Vol.107, pp.48-58
Date published: 12/2017
Publisher: Elsevier Ltd
Academic Unit: Medicine - Infectious Diseases (NJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031654478304646