RePORT India Partners:
- Department of Pathophysiology and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, 05508 São Paulo, Brazil
- Laboratório de Imunoparasitologia, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
- National Institutes of Health- NIRT - International Center for Excellence in Research, Chennai, India
- Unidade de Medicina Investigativa, Laboratório Integrado de Microbiologia e Imunorregulação, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
- Multinational Organization Network Sponsoring Translational and Epidemiological Research, Instituto Brasileiro para a Investigação da Tuberculose, Fundação José Silveira, Salvador, Brazil
- Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil
- Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts United States of America
- National Institute for Research in Tuberculosis, Chennai, India
- Prof. M. Viswanathan Diabetes Research Center, Chennai, India
- Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, USA
Prada-Medina CA, Fukutani KF, Pavan Kumar N, et al. Systems immunology of diabetes-tuberculosis comorbidity reveals signatures of disease complications. Scientific Reports. 2017;7:1999. 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.