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Gene Expression in Cord Blood and Tuberculosis in Early Childhood: A Nested Case-Control Study in a South African
Carly A Bobak1, Maresa Botha2, Lesley Workman2
1Department of Biomedical Data Science, Dartmouth College, Hanover, New Hampshire.
Insights
Gene expression in umbilical cord blood at birth can predict a child's risk for developing tuberculosis (TB) infection or disease later in life. These early molecular signatures offer insights into TB pathogenesis and susceptibility in children.
Area of Science:
- Genomics
- Pediatric Infectious Diseases
- Immunology
Background:
- Transcriptomic profiling is common in adults for tuberculosis (TB) diagnosis and risk prediction.
- Few studies have explored gene expression signatures in children for TB risk identification.
- This study investigated cord blood gene expression for predicting TB outcomes in early childhood.
Purpose of the Study:
- To identify gene expression signatures in umbilical cord blood associated with tuberculin skin test conversion.
- To determine if cord blood gene expression predicts the risk of developing TB disease in the first five years of life.
- To explore novel insights into TB pathogenesis and susceptibility in children.
Main Methods:
- A nested case-control study within the Drakenstein Child Health Study, a South African birth cohort.
- Transcriptome-wide screening of umbilical cord blood samples from 131 neonates.
- Genome-wide RNA expression analysis to identify predictive signatures for tuberculin conversion and TB disease.
Main Results:
- Distinct gene expression signatures differentiated tuberculin conversion (26 genes) and TB disease (10 genes).
- 114 genes correlated with tuberculin conversion and 30 genes with progression to TB disease.
- Coexpression network analysis identified 6 modules linked to TB infection/disease risk, including neutrophil activation and defense against bacteria.
Conclusions:
- Detectable gene expression differences at birth are associated with TB infection and disease risk in early childhood.
- These findings suggest potential for early, blood-based biomarkers for TB risk assessment in neonates.
- Cord blood transcriptomics may offer novel insights into childhood TB pathogenesis and susceptibility.
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.
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