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Impact of intermediate hyperglycaemia as well as diabetes on immune dysfunction in tuberculosis

Eckold, C; Kumar, V; Weiner Rd, J; Alisjahbana, B; Riza, A-L; Ronacher, K; Coronel, J; Kerry-Barnard, S; Malherbe, ST; Kleynhans, L; et al. Eckold, C; Kumar, V; Weiner Rd, J; Alisjahbana, B; Riza, A-L; Ronacher, K; Coronel, J; Kerry-Barnard, S; Malherbe, ST; Kleynhans, L; Stanley, K; Ruslami, R; Ioana, M; Ugarte-Gil, C; Walzl, G; van Crevel, R; Wijmenga, C; Critchley, JA; Dockrell, HM; Cliff, JM (2021) Impact of intermediate hyperglycaemia as well as diabetes on immune dysfunction in tuberculosis. Clin Infect Dis, 72 (1). pp. 69-78. ISSN 1537-6591 https://doi.org/10.1093/cid/ciaa751
SGUL Authors: Critchley, Julia

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Abstract

Background People living with diabetes have an increased risk of developing active tuberculosis and are more likely to have poor tuberculosis-treatment outcomes, which may impact on control of tuberculosis as the prevalence of diabetes is increasing worldwide. Blood transcriptomes are altered in active tuberculosis patients relative to healthy individuals. The effects of diabetes and intermediate hyperglycaemia on this transcriptomic signature were investigated to enhance understanding of immunological susceptibility in diabetes-tuberculosis comorbidity. Methods Whole blood samples were collected from active tuberculosis patients with diabetes (HbA1c ≥6.5%) or intermediate hyperglycaemia (HbA1c 5.7-6.5%), tuberculosis-only patients and healthy controls in four countries: South Africa, Romania, Indonesia and Peru. Differential blood gene expression was determined by RNA-seq (n=249). Results Diabetes increased the magnitude of gene expression change in the host transcriptome in tuberculosis, notably showing an increase in genes associated with innate inflammatory and decrease in adaptive immune responses. Strikingly, patients with intermediate hyperglycaemia and tuberculosis exhibited blood transcriptomes much more similar to diabetes-tuberculosis patients than to patients with only tuberculosis. Both diabetes-tuberculosis and intermediate hyperglycaemia-tuberculosis patients had a decreased type I interferon response relative to tuberculosis-only patients. Conclusions Co-morbidity in individuals with both tuberculosis and diabetes is associated with altered transcriptomes, with an expected enhanced inflammation in the presence of both conditions, but also reduced type 1 interferon responses in co-morbid patients, suggesting an unexpected uncoupling of the TB transcriptome phenotype. These immunological dysfunctions are also present in individuals with intermediate hyperglycaemia, showing that altered immunity to tuberculosis may also be present in this group. The TB disease outcomes in individuals with intermediate hyperglycaemia diagnosed with TB should be investigated further.

Item Type: Article
Additional Information: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. 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, please contact journals.permissions@oup.com
Keywords: Diabetes, Inflammation, Tuberculosis, 06 Biological Sciences, 11 Medical and Health Sciences, Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: Clin Infect Dis
ISSN: 1537-6591
Language: eng
Dates:
DateEvent
1 January 2021Published
13 June 2020Published Online
9 June 2020Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
305279Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
PubMed ID: 32533832
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112001
Publisher's version: https://doi.org/10.1093/cid/ciaa751

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