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Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling

BACKGROUND. Recently acquired and remotely acquired latent Mycobacterium tuberculosis infection (LTBI) are clinically indistinguishable, yet recent acquisition of infection is the greatest risk factor for progression to tuberculosis in immunocompetent individuals. We aimed to evaluate the ability of...

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Autores principales: Halliday, Alice, Whitworth, Hilary, Kottoor, Sherine Hermagild, Niazi, Umar, Menzies, Sarah, Kunst, Heinke, Bremang, Samuel, Badhan, Amarjit, Beverley, Peter, Kon, Onn Min, Lalvani, Ajit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451604/
https://www.ncbi.nlm.nih.gov/pubmed/28329119
http://dx.doi.org/10.1093/infdis/jix107
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author Halliday, Alice
Whitworth, Hilary
Kottoor, Sherine Hermagild
Niazi, Umar
Menzies, Sarah
Kunst, Heinke
Bremang, Samuel
Badhan, Amarjit
Beverley, Peter
Kon, Onn Min
Lalvani, Ajit
author_facet Halliday, Alice
Whitworth, Hilary
Kottoor, Sherine Hermagild
Niazi, Umar
Menzies, Sarah
Kunst, Heinke
Bremang, Samuel
Badhan, Amarjit
Beverley, Peter
Kon, Onn Min
Lalvani, Ajit
author_sort Halliday, Alice
collection PubMed
description BACKGROUND. Recently acquired and remotely acquired latent Mycobacterium tuberculosis infection (LTBI) are clinically indistinguishable, yet recent acquisition of infection is the greatest risk factor for progression to tuberculosis in immunocompetent individuals. We aimed to evaluate the ability of cellular immune signatures that differ between active tuberculosis and LTBI to distinguish recently from remotely acquired LTBI. METHODS. Fifty-nine individuals were recruited: 20 had active tuberculosis, 19 had recently acquired LTBI, and 20 had remotely acquired LTBI. The proportion of mycobacteria-specific CD4(+) T cells secreting tumor necrosis factor α (TNF-α) but not interferon γ or interleukin 2 which had a differentiated effector phenotype (TNF-α–only T(EFF)), and the level of CD27 expression on IFN-γ–producing CD4(+) T cells, were detected by flow cytometry. RESULTS. The TNF-α–only T(EFF) signature was significantly higher in the group with recently acquired LTBI, compared with the group with remotely acquired LTBI (P < .0001), and it discriminated between these groups with high sensitivity and specificity, with an area under the curve of 0.87. Two signatures incorporating CD27 expression did not distinguish between recently and remotely acquired LTBI. Interestingly, the TNF-α–only T(EFF) signature in participants with recently acquired LTBI was more similar to that in participants with tuberculosis than that in participants with remotely acquired LTBI, suggesting that recently acquired LTBI is immunologically more similar to tuberculosis than remotely acquired LTBI. CONCLUSIONS. These findings reveal marked biological heterogeneity underlying the clinically homogeneous phenotype of LTBI, providing a rationale for immunological risk stratification to improve targeting of LTBI treatment.
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spelling pubmed-54516042017-06-05 Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling Halliday, Alice Whitworth, Hilary Kottoor, Sherine Hermagild Niazi, Umar Menzies, Sarah Kunst, Heinke Bremang, Samuel Badhan, Amarjit Beverley, Peter Kon, Onn Min Lalvani, Ajit J Infect Dis Major Article BACKGROUND. Recently acquired and remotely acquired latent Mycobacterium tuberculosis infection (LTBI) are clinically indistinguishable, yet recent acquisition of infection is the greatest risk factor for progression to tuberculosis in immunocompetent individuals. We aimed to evaluate the ability of cellular immune signatures that differ between active tuberculosis and LTBI to distinguish recently from remotely acquired LTBI. METHODS. Fifty-nine individuals were recruited: 20 had active tuberculosis, 19 had recently acquired LTBI, and 20 had remotely acquired LTBI. The proportion of mycobacteria-specific CD4(+) T cells secreting tumor necrosis factor α (TNF-α) but not interferon γ or interleukin 2 which had a differentiated effector phenotype (TNF-α–only T(EFF)), and the level of CD27 expression on IFN-γ–producing CD4(+) T cells, were detected by flow cytometry. RESULTS. The TNF-α–only T(EFF) signature was significantly higher in the group with recently acquired LTBI, compared with the group with remotely acquired LTBI (P < .0001), and it discriminated between these groups with high sensitivity and specificity, with an area under the curve of 0.87. Two signatures incorporating CD27 expression did not distinguish between recently and remotely acquired LTBI. Interestingly, the TNF-α–only T(EFF) signature in participants with recently acquired LTBI was more similar to that in participants with tuberculosis than that in participants with remotely acquired LTBI, suggesting that recently acquired LTBI is immunologically more similar to tuberculosis than remotely acquired LTBI. CONCLUSIONS. These findings reveal marked biological heterogeneity underlying the clinically homogeneous phenotype of LTBI, providing a rationale for immunological risk stratification to improve targeting of LTBI treatment. Oxford University Press 2017-05-01 2017-02-28 /pmc/articles/PMC5451604/ /pubmed/28329119 http://dx.doi.org/10.1093/infdis/jix107 Text en © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Major Article
Halliday, Alice
Whitworth, Hilary
Kottoor, Sherine Hermagild
Niazi, Umar
Menzies, Sarah
Kunst, Heinke
Bremang, Samuel
Badhan, Amarjit
Beverley, Peter
Kon, Onn Min
Lalvani, Ajit
Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling
title Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling
title_full Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling
title_fullStr Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling
title_full_unstemmed Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling
title_short Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling
title_sort stratification of latent mycobacterium tuberculosis infection by cellular immune profiling
topic Major Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451604/
https://www.ncbi.nlm.nih.gov/pubmed/28329119
http://dx.doi.org/10.1093/infdis/jix107
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