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

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dc.contributor.authorEckold, Clareen_ZA
dc.contributor.authorKumar, Vinoden_ZA
dc.contributor.authorWeiner, Januaryen_ZA
dc.contributor.authorAlisjahbana, Bachtien_ZA
dc.contributor.authorRiza, Anca-Leliaen_ZA
dc.contributor.authorRonacher, Katharinaen_ZA
dc.contributor.authorCoronel, Jorgeen_ZA
dc.contributor.authorKerry-Barnard, Sarahen_ZA
dc.contributor.authorMalherbe, Stephanus T.en_ZA
dc.contributor.authorKleynhans, Leanieen_ZA
dc.contributor.authorStanley, Kimen_ZA
dc.contributor.authorRuslami, Rovinaen_ZA
dc.contributor.authorIoana, Mihaien_ZA
dc.contributor.authorUgarte-Gil, Cesaren_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorvan Crevel, Reinouten_ZA
dc.contributor.authorWijmenga, Ciscaen_ZA
dc.contributor.authorCritchley, Julia A.en_ZA
dc.contributor.authorDockrell, Hazel M.en_ZA
dc.contributor.authorCliff, Jacqueline M.en_ZA
dc.date.accessioned2022-06-03T10:06:05Zen_ZA
dc.date.available2022-06-03T10:06:05Zen_ZA
dc.date.issued2020-01en_ZA
dc.descriptionCITATION: Eckold, C., et al. Impact of intermediate hyperglycaemia as well as diabetes on immune dysfunction in tuberculosis. Clinical Infectious Diseases, 72(1):69-78. doi:10.1093/cid/ciaa751en_ZA
dc.descriptionThe original publication is available at https://academic.oup.com/cid/en_ZA
dc.description.abstractBackground: People with diabetes have an increased risk of developing active tuberculosis (TB) and are more likely to have poor TB-treatment outcomes, which may impact on control of TB as the prevalence of diabetes is increasing worldwide. Blood transcriptomes are altered in patients with active TB relative to healthy individuals. The effects of diabetes and intermediate hyperglycemia (IH) on this transcriptomic signature were investigated to enhance understanding of immunological susceptibility in diabetes-TB comorbidity. Methods: Whole blood samples were collected from active TB patients with diabetes (glycated hemoglobin [HbA1c] ≥6.5%) or IH (HbA1c = 5.7% to <6.5%), TB-only patients, and healthy controls in 4 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 TB, notably showing an increase in genes associated with innate inflammatory and decrease in adaptive immune responses. Strikingly, patients with IH and TB exhibited blood transcriptomes much more similar to patients with diabetes-TB than to patients with only TB. Both diabetes-TB and IH-TB patients had a decreased type I interferon response relative to TB-only patients. Conclusions: Comorbidity in individuals with both TB and diabetes is associated with altered transcriptomes, with an expected enhanced inflammation in the presence of both conditions, but also reduced type I interferon responses in comorbid patients, suggesting an unexpected uncoupling of the TB transcriptome phenotype. These immunological dysfunctions are also present in individuals with IH, showing that altered immunity to TB may also be present in this group. The TB disease outcomes in individuals with IH diagnosed with TB should be investigated further.en_ZA
dc.description.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823074/en_ZA
dc.description.versionPublishers versionen_ZA
dc.format.extent10 pagesen_ZA
dc.identifier.citationEckold, C., et al. Impact of intermediate hyperglycaemia as well as diabetes on immune dysfunction in tuberculosis. Clinical Infectious Diseases, 72(1):69-78. doi:10.1093/cid/ciaa751en_ZA
dc.identifier.issn1537-6591 (online)en_ZA
dc.identifier.issn1058-4838 (print)en_ZA
dc.identifier.otherdoi:10.1093/cid/ciaa751en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/125312en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherOxford University Pressen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectDiabetes -- Complicationsen_ZA
dc.subjectHyperglycemiaen_ZA
dc.subjectImmune responseen_ZA
dc.subjectTuberculosis -- Immunological aspectsen_ZA
dc.subjectInflammation -- Immunological aspectsen_ZA
dc.titleImpact of intermediate hyperglycaemia as well as diabetes on immune dysfunction in tuberculosisen_ZA
dc.typeArticleen_ZA
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