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http://bura.brunel.ac.uk/handle/2438/27160
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DC Field | Value | Language |
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dc.contributor.author | Eckold, C | - |
dc.contributor.author | van Doorn, CLR | - |
dc.contributor.author | Ruslami, R | - |
dc.contributor.author | Ronacher, K | - |
dc.contributor.author | Riza, A | - |
dc.contributor.author | van Veen, S | - |
dc.contributor.author | Lee, J | - |
dc.contributor.author | Kumar, V | - |
dc.contributor.author | Kerry‐Barnard, S | - |
dc.contributor.author | Malherbe, ST | - |
dc.contributor.author | Kleynhans, L | - |
dc.contributor.author | Stanley, K | - |
dc.contributor.author | Joosten, SA | - |
dc.contributor.author | Critchley, JA | - |
dc.contributor.author | Hill, PC | - |
dc.contributor.author | van Crevel, R | - |
dc.contributor.author | Wijmenga, C | - |
dc.contributor.author | Haks, MC | - |
dc.contributor.author | Ioana, M | - |
dc.contributor.author | Alisjahbana, B | - |
dc.contributor.author | Walzl, G | - |
dc.contributor.author | Ottenhoff, THM | - |
dc.contributor.author | Dockrell, HM | - |
dc.contributor.author | Vianello, E | - |
dc.contributor.author | Cliff, JM | - |
dc.contributor.other | TANDEM Consortium | - |
dc.date.accessioned | 2023-09-12T08:01:08Z | - |
dc.date.available | 2023-09-12T08:01:08Z | - |
dc.date.issued | 2023-08-30 | - |
dc.identifier | ORCID iDs: .Ji-Sook Lee https://orcid.org/0000-0003-1747-9700; Jacqueline M. Cliff https://orcid.org/0000-0002-5653-1818 | - |
dc.identifier | e1375 | - |
dc.identifier.citation | Eckold, C. et al. for the TANDEM Consortium (2023) 'Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity', Clinical and Translational Medicine, 13 (9), e1375, pp. 1 - 19. doi: 10.1002/ctm2.1375. | en_US |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/27160 | - |
dc.description | Clare Eckold and Cassandra L.R. van Doorn contributed equally to this manuscript. Eleonora Vianello and Jacqueline M. Cliff contributed equally to this manuscript. | en_US |
dc.description | Data availability statement: The data that support the RNA-Seq findings of this study are openly available in NCBI-GEO at https://www.ncbi.nlm.nih.gov/geo/, accession number GSE193978. The data that support the dcRT-MLPA findings of this study are available in the supplementary material of this article. | - |
dc.description.abstract | Copyright © 2023 The Authors. Background: People with diabetes are more likely to develop tuberculosis (TB) and to have poor TB-treatment outcomes than those without. We previously showed that blood transcriptomes in people with TB-diabetes (TB-DM) co-morbidity have excessive inflammatory and reduced interferon responses at diagnosis. It is unknown whether this persists through treatment and contributes to the adverse outcomes. Methods: Pulmonary TB patients recruited in South Africa, Indonesia and Romania were classified as having TB-DM, TB with prediabetes, TB-related hyperglycaemia or TB-only, based on glycated haemoglobin concentration at TB diagnosis and after 6 months of TB treatment. Gene expression in blood at diagnosis and intervals throughout treatment was measured by unbiased RNA-Seq and targeted Multiplex Ligation-dependent Probe Amplification. Transcriptomic data were analysed by longitudinal mixed-model regression to identify whether genes were differentially expressed between clinical groups through time. Predictive models of TB-treatment response across groups were developed and cross-tested. Results: Gene expression differed between TB and TB-DM patients at diagnosis and was modulated by TB treatment in all clinical groups but to different extents, such that differences remained in TB-DM relative to TB-only throughout. Expression of some genes increased through TB treatment, whereas others decreased: some were persistently more highly expressed in TB-DM and others in TB-only patients. Genes involved in innate immune responses, anti-microbial immunity and inflammation were significantly upregulated in people with TB-DM throughout treatment. The overall pattern of change was similar across clinical groups irrespective of diabetes status, permitting models predictive of TB treatment to be developed. Conclusions: Exacerbated transcriptome changes in TB-DM take longer to resolve during TB treatment, meaning they remain different from those in uncomplicated TB after treatment completion. This may indicate a prolonged inflammatory response in TB-DM, requiring prolonged treatment or host-directed therapy for complete cure. Development of transcriptome-based biomarker signatures of TB-treatment response should include people with diabetes for use across populations. | en_US |
dc.description.sponsorship | European Community's Seventh Framework Programme. Grant Number: 305279; Netherlands Organization for Scientific Research. Grant Number: 91214038 | en_US |
dc.format.extent | 1 - 19 | - |
dc.format.medium | Electronic | - |
dc.language | English | - |
dc.language.iso | en | en_US |
dc.publisher | Wiley on behalf of Shanghai Institute of Clinical Bioinformatics | en_US |
dc.relation.uri | https://www.medrxiv.org/content/10.1101/2022.02.07.22269422v1 | - |
dc.rights | Copyright © 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject | diabetes | en_US |
dc.subject | transcriptome | en_US |
dc.subject | treatment | en_US |
dc.subject | tuberculosis | en_US |
dc.title | Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity | en_US |
dc.type | Article | en_US |
dc.identifier.doi | https://doi.org/10.1002/ctm2.1375 | - |
dc.relation.isPartOf | Clinical and Translational Medicine | - |
pubs.issue | 9 | - |
pubs.publication-status | Published | - |
pubs.volume | 13 | - |
dc.identifier.eissn | 2001-1326 | - |
dc.rights.holder | The Authors | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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FullText.pdf | Copyright © 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | 4.33 MB | Adobe PDF | View/Open |
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