Gene expression in cord blood and tuberculosis in early childhood: a nested case-control study in a South African birth cohort
Gene expression in cord blood and tuberculosis in early childhood: a nested case-control study in a South African birth cohort
Background. Transcriptomic profiling of adults with tuberculosis (TB) has become increasingly common, predominantly for diagnostic and risk prediction purposes. However, few studies have evaluated signatures in children, particularly in identifying those at risk for developing TB disease. We investigated the relationship between gene expression obtained from umbilical cord blood and both tuberculin skin test conversion and incident TB disease through the first 5 years of life. Methods. We conducted a nested case-control study in the Drakenstein Child Health Study, a longitudinal, population-based birth cohort in South Africa. We applied transcriptome-wide screens to umbilical cord blood samples from neonates born to a subset of selected mothers (N = 131). Signatures identifying tuberculin conversion and risk of subsequent TB disease were identified from genome-wide analysis of RNA expression. Results. Gene expression signatures revealed clear differences predictive of tuberculin conversion (n = 26) and TB disease (n = 10); 114 genes were associated with tuberculin conversion and 30 genes were associated with the progression to TB disease among children with early infection. Coexpression network analysis revealed 6 modules associated with risk of TB infection or disease, including a module associated with neutrophil activation in immune response (P < .0001) and defense response to bacterium (P < .0001). Conclusions. These findings suggest multiple detectable differences in gene expression at birth that were associated with risk of TB infection or disease throughout early childhood. Such measures may provide novel insights into TB pathogenesis and susceptibility.
pediatrics, transcriptomics, tuberculosis
438-449
Bobak, Carly A.
a78153e1-a72d-4703-8a13-8b3201058811
Botha, Maresa
38d5ad5b-215c-4ac5-a5da-046459d1be80
Workman, Lesley
a24c8ceb-b922-450a-b84a-f6099011b2ee
Hill, Jane E.
63e1f8f0-a859-4cd1-b3d6-170ac23770c7
Nicol, Mark
a4f984dd-458f-436b-bb4f-ec3470f5977e
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Stein, Dan J.
3f838c91-d004-4a8e-bee5-88af65cf9d2d
Martinez, Leonardo
ac2e65ef-2401-4949-8607-a249d33d07dd
Zar, Heather J.
a00ab263-ace5-4d01-8ec6-23f5b8f09f8d
1 August 2023
Bobak, Carly A.
a78153e1-a72d-4703-8a13-8b3201058811
Botha, Maresa
38d5ad5b-215c-4ac5-a5da-046459d1be80
Workman, Lesley
a24c8ceb-b922-450a-b84a-f6099011b2ee
Hill, Jane E.
63e1f8f0-a859-4cd1-b3d6-170ac23770c7
Nicol, Mark
a4f984dd-458f-436b-bb4f-ec3470f5977e
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Stein, Dan J.
3f838c91-d004-4a8e-bee5-88af65cf9d2d
Martinez, Leonardo
ac2e65ef-2401-4949-8607-a249d33d07dd
Zar, Heather J.
a00ab263-ace5-4d01-8ec6-23f5b8f09f8d
Bobak, Carly A., Botha, Maresa, Workman, Lesley, Hill, Jane E., Nicol, Mark, Holloway, John W., Stein, Dan J., Martinez, Leonardo and Zar, Heather J.
(2023)
Gene expression in cord blood and tuberculosis in early childhood: a nested case-control study in a South African birth cohort.
Clinical Infectious Diseases, 77 (3), , [ciad268].
(doi:10.1093/cid/ciad268).
Abstract
Background. Transcriptomic profiling of adults with tuberculosis (TB) has become increasingly common, predominantly for diagnostic and risk prediction purposes. However, few studies have evaluated signatures in children, particularly in identifying those at risk for developing TB disease. We investigated the relationship between gene expression obtained from umbilical cord blood and both tuberculin skin test conversion and incident TB disease through the first 5 years of life. Methods. We conducted a nested case-control study in the Drakenstein Child Health Study, a longitudinal, population-based birth cohort in South Africa. We applied transcriptome-wide screens to umbilical cord blood samples from neonates born to a subset of selected mothers (N = 131). Signatures identifying tuberculin conversion and risk of subsequent TB disease were identified from genome-wide analysis of RNA expression. Results. Gene expression signatures revealed clear differences predictive of tuberculin conversion (n = 26) and TB disease (n = 10); 114 genes were associated with tuberculin conversion and 30 genes were associated with the progression to TB disease among children with early infection. Coexpression network analysis revealed 6 modules associated with risk of TB infection or disease, including a module associated with neutrophil activation in immune response (P < .0001) and defense response to bacterium (P < .0001). Conclusions. These findings suggest multiple detectable differences in gene expression at birth that were associated with risk of TB infection or disease throughout early childhood. Such measures may provide novel insights into TB pathogenesis and susceptibility.
Text
Manuscript_NoHighlightVersion
- Accepted Manuscript
Text
ciad268
- Version of Record
More information
Accepted/In Press date: 29 April 2023
e-pub ahead of print date: 5 May 2023
Published date: 1 August 2023
Additional Information:
Funding Information:
Potential conflicts of interest. D. J. S. reports grants or contracts from the United Kingdom MRC; royalties or licenses from American Psychiatric Press, Cambridge University Press, and Elsevier/Academic Press; consulting fees (paid to author) from Discovery Vitality, Kanna, Lundbeck, Orion, Sanofi, and Vistagen; payment or honoraria (directly to author) from Johnson & Johnson, L’Oreal, Servier, and Takeda; meeting and/or travel support from Lundbeck and Servier; and a role on a board, society, or committee for the African College of Neuropsychopharmacology. J. E. H. reports grants from the NIH, Bill & Melinda Gates Foundation, Cystic Fibrosis Foundation, National Sciences and Engineering Research Council of Canada, Australian Research Council, and Canada Research Chair Program; and received nonfinancial support (equipment, materials, or drugs) from Shimadzu and Markes International. C. A. B. reports consulting fees from ModernaTX (paid to institution for unrelated work). All other authors report no potential conflicts.
Funding Information:
Financial support. This work was funded by the Bill & Melinda Gates Foundation (grant number OPP 1017641); South African Medical Research Council (MRC); the National Research Foundation (South Africa); and the Wellcome Trust. C. A. B. was supported by the Burroughs Wellcome Fund institutional program grant unifying population- and laboratory-based sciences to Dartmouth College (grant number 1014106). J. E. H. received support from Dartmouth College and reports grants from the US National Institutes of Health (NIH), the US Cystic Fibrosis Foundation, the Australian Research Council, and the National Sciences and Engineering Research Council of Canada during the completion of this study. H. J. Z. reports grants from the Bill & Melinda Gates Foundation, the NIH, the Wellcome Trust UK, and the MRC South Africa, National Research Foundation (South Africa), during completion of the study. D. J. S. reports support from NIH and MRC South Africa. L. W. received support from the Bill & Melinda Gates Foundation (grant number OPP 1017641) and the MRC South Africa, National Research Foundation South Africa. M. N. was supported by the Bill & Melinda Gates Foundation and the Australian National Health and Medical Research Council (grant number 1174455; payments made to institution). L.M. was funded by the National Institutes of Health (grant number 5K01AI156022).
Publisher Copyright:
© The Author(s) 2023.
Keywords:
pediatrics, transcriptomics, tuberculosis
Identifiers
Local EPrints ID: 476895
URI: http://eprints.soton.ac.uk/id/eprint/476895
ISSN: 1058-4838
PURE UUID: 0149f072-0633-4d3c-8332-c45ca9b95414
Catalogue record
Date deposited: 18 May 2023 16:59
Last modified: 10 Aug 2024 01:35
Export record
Altmetrics
Contributors
Author:
Carly A. Bobak
Author:
Maresa Botha
Author:
Lesley Workman
Author:
Jane E. Hill
Author:
Mark Nicol
Author:
Dan J. Stein
Author:
Leonardo Martinez
Author:
Heather J. Zar
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
