Background:
Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB), increasing the risk of active disease, treatment failure, and death. While individuals with TB-DM comorbidity are known to exhibit higher systemic inflammation and distinct cytokine profiles, a comprehensive understanding of the underlying gene expression changes in these patients is missing. Systematically identifying these transcriptomic signatures could provide insights into the biological mechanisms of the TB-DM interaction and help identify potential biomarkers for diagnosis and treatment monitoring.
Abstract:
Objective: To synthesize available evidence on host blood transcriptomic profiles in individuals with TB-DM comorbidity compared to TB alone or healthy controls.
Methods: A systematic review and meta-analysis were performed following PRISMA guidelines. Studies assessing whole blood or peripheral blood mononuclear cell gene expression via microarray or RNA-sequencing in TB-DM patients were included. Meta-analysis identified differentially expressed genes (DEGs) and enriched biological pathways.
Results: TB-DM patients exhibited a unique transcriptomic signature characterized by the upregulation of genes involved in innate immune activation, such as interferon-stimulated genes (ISGs) and neutrophil-associated pathways. Conversely, genes related to adaptive immunity, particularly T-cell signaling and function, were frequently downregulated compared to patients with TB alone. These changes were more pronounced in individuals with poor glycemic control.
Conclusion: The TB-DM comorbidity is defined by a distinct transcriptomic imprinting characterized by exacerbated innate inflammation and impaired adaptive immune responses. These findings highlight specific molecular pathways that could be targeted for host-directed therapies to improve TB outcomes in diabetic patients.
Keywords: Tuberculosis, Diabetes mellitus, Transcriptome, Meta-analysis, Gene expression, Inflammation.
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- Data de Publicação: 04/12/2019
- Autores: Jeffrey A. Tornheim,1, Anil K. Madugundu,2,3,4,5 Mandar Paradkar,6 Kiyoshi F. Fukutani,7,8,9 Artur T. L. Queiroz,7,8 Nikhil Gupte,1,6 Akshay N. Gupte,1 Aarti Kinikar,10 Vandana Kulkarni,6 Usha Balasubramanian,6 Sreelakshmi Sreenivasamurthy,2,3,11 Remya Raja,2,3,4 Neeta Pradhan,6 Shri Vijay Bala Yogendra Shivakumar,12 Chhaya Valvi,10 Luke Elizabeth Hanna,13 Bruno B. Andrade,7,8,9,14,15,a Vidya Mave,1,6 Akhilesh Pandey,2,3,5,11,a and Amita Gupta1,16, ; for the CTRIUMPh RePORT India Study Team
