Transcriptomics for child and adolescent tuberculosis
Myrsini Kaforou1, Claire Broderick1, Ortensia Vito1
1Department of Infectious Disease, Imperial College London, London, UK.
Insights
Transcriptomics in children reveals blood gene expression markers for diagnosing tuberculosis (TB) and predicting its progression. These findings are crucial for developing new diagnostic tools for pediatric TB.
Area of Science:
- Pediatric Infectious Diseases
- Molecular Biology
- Immunology
Background:
- Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), significantly impacts children, with unique disease progression and mortality risks.
- Pediatric TB presents distinct challenges in diagnostics, therapeutics, and vaccine development compared to adults.
- Host and pathogen factors, particularly age, influence TB infection progression and outcomes.
Purpose of the Study:
- To review the role of transcriptomics in understanding pediatric and adolescent tuberculosis.
- To highlight the potential of blood gene expression profiling for biomarker discovery in pediatric TB.
- To assess the utility of transcriptomics in diagnosing TB, predicting disease progression, and monitoring treatment response in young populations.
Main Methods:
- Utilizing high-throughput methods like RNA-Sequencing and microarray analysis to quantify RNA transcripts in peripheral blood.
- Analyzing gene expression profiles to understand host immune responses to Mtb infection and disease.
- Focusing on studies specifically investigating pediatric and adolescent populations.
Main Results:
- Gene expression profiling in blood has identified potential diagnostic and prognostic biomarkers for pediatric TB.
- Identified blood gene expression markers meet or exceed current sensitivity and specificity targets for diagnostic tools.
- Transcriptomic signatures show promise for discriminating disease states and aiding clinical decision-making.
Conclusions:
- Transcriptomics offers a powerful, hypothesis-free approach to unraveling pediatric TB biology.
- Blood-based gene expression signatures are emerging as valuable tools for diagnosing and managing TB in children and adolescents.
- Ongoing translation of these transcriptomic findings into clinical diagnostic tests is anticipated.
Abstract:
Tuberculosis (TB) in humans is caused by Mycobacterium tuberculosis (Mtb). It is estimated that 70 million children (<15 years) are currently infected with Mtb, with 1.2 million each year progressing to disease. Of these, a quarter die. The risk of progression from Mtb infection to disease and from disease to death is dependent on multiple pathogen and host factors. Age is a central component in all these transitions. The natural history of TB in children and adolescents is different to adults, leading to unique challenges in the development of diagnostics, therapeutics, and vaccines. The quantification of RNA transcripts in specific cells or in the peripheral blood, using high-throughput methods, such as microarray analysis or RNA-Sequencing, can shed light into the host immune response to Mtb during infection and disease, as well as understanding treatment response, disease severity, and vaccination, in a global hypothesis-free manner. Additionally, gene expression profiling can be used for biomarker discovery, to diagnose disease, predict future disease progression and to monitor response to treatment. Here, we review the role of transcriptomics in children and adolescents, focused mainly on work done in blood, to understand disease biology, and to discriminate disease states to assist clinical decision-making. In recent years, studies with a specific pediatric and adolescent focus have identified blood gene expression markers with diagnostic or prognostic potential that meet or exceed the current sensitivity and specificity targets for diagnostic tools. Diagnostic and prognostic gene expression signatures identified through high-throughput methods are currently being translated into diagnostic tests.
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