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 adult tuberculosis patients 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 as well as incident tuberculosis 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 tuberculosis disease were identified from genome wide analysis of RNA expression.
Results: gene expression signatures revealed clear differences predictive of tuberculin conversion (n=26) and tuberculosis disease (n=10); 114 genes were associated with tuberculin conversion and 30 genes were associated with the progression to tuberculosis disease among children with early infection. Co-expression network analysis revealed six modules associated with risk of tuberculosis infection or disease, including a module associated with neutrophil activation in immune response (p<0.0001) and defense response to bacterium (p<0.0001).
Conclusions: these findings suggest multiple detectable differences in gene expression at birth which were associated with risk of tuberculosis infection or disease throughout early childhood. Such measures may provide novel insights into tuberculosis pathogenesis and susceptibility.
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
14 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 adult tuberculosis patients 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 as well as incident tuberculosis 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 tuberculosis disease were identified from genome wide analysis of RNA expression.
Results: gene expression signatures revealed clear differences predictive of tuberculin conversion (n=26) and tuberculosis disease (n=10); 114 genes were associated with tuberculin conversion and 30 genes were associated with the progression to tuberculosis disease among children with early infection. Co-expression network analysis revealed six modules associated with risk of tuberculosis infection or disease, including a module associated with neutrophil activation in immune response (p<0.0001) and defense response to bacterium (p<0.0001).
Conclusions: these findings suggest multiple detectable differences in gene expression at birth which were associated with risk of tuberculosis infection or disease throughout early childhood. Such measures may provide novel insights into tuberculosis pathogenesis and susceptibility.
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Accepted/In Press date: 29 April 2023
e-pub ahead of print date: 5 May 2023
Published date: 14 August 2023
Identifiers
Local EPrints ID: 476895
URI: http://eprints.soton.ac.uk/id/eprint/476895
ISSN: 1058-4838
PURE UUID: 0149f072-0633-4d3c-8332-c45ca9b95414
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Date deposited: 18 May 2023 16:59
Last modified: 19 Aug 2023 01:34
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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
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