Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications
Authors
Prada-Medina, Cesar A.Fukutani, Kiyoshi F.
Pavan Kumar, Nathella
Gil-Santana, Leonardo
Babu, Subash
Lichtenstein, Flavio
West, Kim
Sivakumar, Shanmugam
Menon, Pradeep A.
Viswanathan, Vijay
Andrade, Bruno B.
Nakaya, Helder I.
Kornfeld, Hardy
UMass Chan Affiliations
Department of Medicine, Division of Pulmonary Allergy and Critical Care MedicineDocument Type
Journal ArticlePublication Date
2017-05-17Keywords
Diabetes complicationsTuberculosis
Endocrinology, Diabetes, and Metabolism
Immunology of Infectious Disease
Immunopathology
Integrative Biology
Systems Biology
Metadata
Show full item recordAbstract
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.Source
Sci Rep. 2017 May 17;7(1):1999. doi: 10.1038/s41598-017-01767-4. Link to article on publisher's siteDOI
10.1038/s41598-017-01767-4Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40357PubMed ID
28515464Related Resources
Rights
Copyright © The Author(s) 2017Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1038/s41598-017-01767-4