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DC Field | Value | Language |
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dc.contributor.author | Cliff, JM | - |
dc.contributor.author | Cho, JE | - |
dc.contributor.author | Lee, JS | - |
dc.contributor.author | Ronacher, K | - |
dc.contributor.author | King, EC | - |
dc.contributor.author | Van Helden, P | - |
dc.contributor.author | Walzl, G | - |
dc.contributor.author | Dockrell, HM | - |
dc.date.accessioned | 2023-12-14T15:20:06Z | - |
dc.date.available | 2016-02-01 | - |
dc.date.available | 2023-12-14T15:20:06Z | - |
dc.date.issued | 2015-09-07 | - |
dc.identifier | ORCiD ID: Jackie Cliff https://orcid.org/0000-0002-5653-1818 | - |
dc.identifier | ORCiD ID: Ji Sook LEE https://orcid.org/0000-0003-1747-9700 | - |
dc.identifier | ORCiD ID: Katharina Ronacher https://orcid.org/0000-0002-6371-1462 | - |
dc.identifier | ORCiD ID: Gerhard Walzl https://orcid.org/0000-0003-2487-125X | - |
dc.identifier | ORCiD ID: Hazel Dockrell https://orcid.org/0000-0003-1869-9107 | - |
dc.identifier.citation | Cliff, J.M. et al. (2015) 'Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment', The Journal of infectious diseases, 213 (3), pp. 485 - 495. doi: 10.1093/infdis/jiv447. | en_US |
dc.identifier.issn | 0022-1899 | - |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/27855 | - |
dc.description | Supplementary data are available online (zip file) at: https://doi.org/10.1093/infdis/jiv447 . | en_US |
dc.description.abstract | Background. Currently, there are no tools to accurately predict tuberculosis relapse. This study aimed to determine whether patients who experience tuberculosis relapse have different immune responses to mycobacteria in vitro than patients who remain cured for 2 years. Methods. Patients with an initial episode of pulmonary tuberculosis were recruited in South Africa. Diluted blood, collected at diagnosis and after 2 and 4 weeks of treatment, was cultured with live Mycobacterium tuberculosis for 6 days, and cellular RNA was frozen. Gene expression in samples from 10 patients who subsequently experienced relapse, confirmed by strain genotyping, was compared to that in samples from patients who remained cured, using microarrays. Results. At diagnosis, expression of 668 genes was significantly different in samples from patients who experienced relapse, compared with expression in patients who remained successfully cured; these differences persisted for at least 4 weeks. Gene ontology and biological pathways analyses revealed significant upregulation of genes involved in cytotoxic cell-mediated killing. Results were confirmed by real-time quantitative reverse-transcription polymerase chain reaction analysis in a wider patient cohort. Conclusions. These data show that patients who will subsequently experience relapse exhibit altered immune responses, including excessively robust cytolytic responses to M. tuberculosis in vitro, at the time of diagnosis, compared with patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited in drug development. | en_US |
dc.description.sponsorship | GlaxoSmithKline Action TB, the European and Developing Countries Clinical Trials Partnership (grants IP. 09.32040.011 and 2004.1.R.d1), the Bill and Melinda Gates Foundation (grant 48941), and EU-FP7 (TANDEM: grant 305279) | en_US |
dc.format.extent | 485 - 495 | - |
dc.format.medium | Print-Electronic | - |
dc.publisher | Oxford University Press | en_US |
dc.rights | Copyright © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, contact journals.permissions@oup.com. | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | - |
dc.subject | transcriptomics | en_US |
dc.subject | microarray | en_US |
dc.subject | drug development | en_US |
dc.subject | blood | en_US |
dc.subject | patient | en_US |
dc.title | Excessive cytolytic responses predict tuberculosis relapse after apparently successful treatment | en_US |
dc.type | Article | en_US |
dc.identifier.doi | https://doi.org/10.1093/infdis/jiv447 | - |
dc.relation.isPartOf | Journal of Infectious Diseases | - |
pubs.issue | 3 | - |
pubs.publication-status | Published | - |
pubs.volume | 213 | - |
dc.identifier.eissn | 1537-6613 | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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File | Description | Size | Format | |
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FullText.pdf | Copyright © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, contact journals.permissions@oup.com. | 1.02 MB | Adobe PDF | View/Open |
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