Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications

• Published in: Scientific reports Vol. 7; no. 1; pp. 1999 - 16
• Main Authors: Prada-Medina, Cesar A., Fukutani, Kiyoshi F., Pavan Kumar, Nathella, Gil-Santana, Leonardo, Babu, Subash, Lichtenstein, Flávio, West, Kim, Sivakumar, Shanmugam, Menon, Pradeep A., Viswanathan, Vijay, Andrade, Bruno B., Nakaya, Helder I., Kornfeld, Hardy
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.05.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 692/163/2743/137/138; 692/699/255/1856; 82/80; Biomarkers; Body mass index; Cholesterol; Clinical trials; Comorbidity; Computational Biology - methods; Cytokines; Cytokines - blood; Cytokines - metabolism; Diabetes; Diabetes Complications; Diabetes mellitus; Diabetes Mellitus - epidemiology; Diabetes Mellitus - genetics; Diabetes Mellitus - immunology; Diabetes Mellitus - metabolism; Disease Susceptibility; Female; Gene expression; Gene Expression Profiling; Growth factors; High density lipoprotein; Humanities and Social Sciences; Humans; Immunity - genetics; Immunology; India - epidemiology; Leukocytes (neutrophilic); Male; Morbidity; multidisciplinary; Proteome; Proteomics - methods; Public Health Surveillance; Risk Factors; Science; Science (multidisciplinary); Transcription; Transcriptome; Tuberculosis; Tuberculosis - epidemiology; Tuberculosis - genetics; Tuberculosis - immunology; Tuberculosis - metabolism; India
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-01767-4

Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM. Neutrophil count correlated with the molecular degree of perturbation, especially in TBDM patients. Body mass index and HDL cholesterol were negatively correlated with molecular degree of perturbation. Diabetic complication pathways including several pathways linked to epigenetic reprogramming were activated in TBDM above levels observed with DM alone. Our data provide a rationale for trials of host-directed therapies in TBDM, targeting neutrophilic inflammation and diabetic complication pathways to address the greater morbidity and mortality associated with this increasingly prevalent dual burden of communicable and non-communicable diseases.