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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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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. |
format | Online Article Text |
id | pubmed-5451604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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