Journal
CLINICAL INFECTIOUS DISEASES
Volume -, Issue -, Pages -Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciad268
Keywords
tuberculosis; pediatrics; transcriptomics
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This study investigated the relationship between gene expression in umbilical cord blood and the risk of developing tuberculosis (TB) infection and disease in early life. Gene expression signatures were identified that were predictive of TB conversion and progression to TB disease in children with early infection. Coexpression network analysis revealed modules associated with neutrophil activation and defense responses to bacteria. These findings provide novel insights into 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. Gene expression in umbilical cord blood demonstrates associations with tuberculosis infection and disease in early life. Differentially expressed genes overlap with known diagnosis and risk signatures. Implicated biological mechanisms include neutrophil activation and defense responses to bacteria.
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