The value of transcriptomics in advancing knowledge of the immune response and diagnosis in tuberculosis

ABSTRACT Blood transcriptomics analysis of tuberculosis has revealed an interferon-inducible gene signature that diminishes in expression after successful treatment; this promises improved

diagnostics and treatment monitoring, which are essential for the eradication of tuberculosis. Sensitive radiography revealing lung abnormalities and blood transcriptomics have demonstrated

heterogeneity in patients with active tuberculosis and exposed asymptomatic people with latent tuberculosis, suggestive of a continuum of infection and immune states. Here we describe the

immune response to infection with _Mycobacterium tuberculosis_ revealed through the use of transcriptomics, as well as differences among clinical phenotypes of infection that might provide

information on temporal changes in host immunity associated with evolving infection. We also review the diverse blood transcriptional signatures, composed of small sets of genes, that have

been proposed for the diagnosis of tuberculosis and the identification of at-risk asymptomatic people and suggest novel approaches for the development of such biomarkers for clinical use.

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OTHERS COMPARATIVE TRANSCRIPTOMIC ANALYSIS OF WHOLE BLOOD MYCOBACTERIAL GROWTH ASSAYS AND TUBERCULOSIS PATIENTS’ BLOOD RNA PROFILES Article Open access 21 October 2022 IDENTIFICATION OF

IMMUNE BIOMARKERS IN RECENT ACTIVE PULMONARY TUBERCULOSIS Article Open access 17 July 2023 IDENTIFICATION OF IMMUNE PHENOTYPES AND DIAGNOSTIC BIOMARKERS IN ACTIVE AND LATENT TUBERCULOSIS

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Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS A.S., R.J.W. and A.O.G. were funded by The Francis Crick Institute (Crick 10126 and Crick 10468 for

A.O.G. and A.S., and Crick 10128 for R.J.W.), which receives its core funding from Cancer Research UK, the UK Medical Research Council and the Wellcome Trust. R.J.W. was supported by the

Wellcome Trust (104803 and 203135); MRC South Africa under strategic health innovation partnerships EDCTP SR1A 2015-1065 and the US National Institutes of Health (019 AI 111276 and

UO1AI115940). P.H. was supported by NIHR Leicester Biomedical Research Centre and the University of Leicester. M.R. was supported by Medical Diagnostic Discovery Department, bioMérieux SA,

Marcy l’Etoile, France. The views expressed are those of the author(s) and not necessarily those of the NHS the NIHR or the Department of Health. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS

* Laboratory of Immunoregulation and Infection, The Francis Crick Institute, London, UK Akul Singhania & Anne O’Garra * Laboratory of Tuberculosis, The Francis Crick Institute, London,

UK Robert J. Wilkinson * Department of Medicine, Imperial College London, London, UK Robert J. Wilkinson * Wellcome Centre for Infectious Diseases Research in Africa, University of Cape

Town, Observatory, 7925, Cape Town, Republic of South Africa Robert J. Wilkinson * Medical Diagnostic Discovery Department, bioMerieux SA, Marcy l’Etoile, France Marc Rodrigue * Respiratory

Biomedical Research Centre, Institute for Lung Health, Department of Infection Immunity and Inflammation, University of Leicester, Leicester, UK Pranabashis Haldar * National Heart and Lung

Institute, Imperial College London, London, UK Anne O’Garra Authors * Akul Singhania View author publications You can also search for this author inPubMed Google Scholar * Robert J.

Wilkinson View author publications You can also search for this author inPubMed Google Scholar * Marc Rodrigue View author publications You can also search for this author inPubMed Google

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inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Anne O’Garra. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. Patents previously held by

A.O.G. on the use of the blood transcriptome for the diagnosis of tuberculosis have lapsed and have been discontinued. M.R. is an employee of BioMérieux, which has not filed patents related

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