Gene Expression in Cord Blood and Tuberculosis in Early Childhood: A Nested Case-Control Study in a South African Birth Cohort

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.

Endotypes of Paediatric Cough—Do They Exist and Finding New Techniques to Improve Clinical Outcomes

“…While these findings were mainly from adult data, the lack of effective host-focused endotyping for paediatric TB is a major shortcoming. A South African, case-control, birth cohort study (The Drakenstein Child Health Study) [51] indirectly addressed this knowledge gap by examining the relationship between gene expression profiles from umbilical cord blood and tuberculin skin test conversion and TB disease in the first five years of life. They found several novel gene expression profiles associated with tuberculin conversion and progression to TB disease among children with early infection, providing novel endotype data in children.…”