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SYSTEMS IMMUNOLOGY OF DIABETES-TUBERCULOSIS COMORBIDITY REVEALS SIGNATURES OF DISEASE COMPLICATIONS
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University of São Paulo. School of Pharmaceutical Sciences. Department of Pathophysiology and Toxicology. São Paulo, SP, Brazil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Imunoparasitologia. Salvador, BA, Brasil
National Institutes of Health- NIRT. International Center for Excellence in Research. Chennai, India
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação. Unidade de Medicina Investigativa. Salvador, BA, Brasil / Instituto Brasileiro para a Investigação da Tuberculose. Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brazil
National Institutes of Health- NIRT. International Center for Excellence in Research. Chennai, India
University of São Paulo. School of Pharmaceutical Sciences. Department of Pathophysiology and Toxicology. São Paulo, SP, Brazil
University of Massachusetts Medical School. Department of Medicine. Worcester, Massachusetts. USA
National Institute for Research in Tuberculosis. Chennai, India
National Institute for Research in Tuberculosis. Chennai, India
Prof. M. Viswanathan Diabetes Research Center. Chennai, India
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação. Unidade de Medicina Investigativa. Salvador, BA, Brasil / Instituto Brasileiro para a Investigação da Tuberculose. Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brazil / Universidade Salvador. Laureate Universities. Salvador, BA, Brazil / Vanderbilt University School of Medicine. Division of Infectious Diseases. Department of Medicine Nashville. USA
University of São Paulo. School of Pharmaceutical Sciences. Department of Pathophysiology and Toxicology. São Paulo, SP, Brazil
University of Massachusetts Medical School. Department of Medicine. Worcester, Massachusetts, USA
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Imunoparasitologia. Salvador, BA, Brasil
National Institutes of Health- NIRT. International Center for Excellence in Research. Chennai, India
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação. Unidade de Medicina Investigativa. Salvador, BA, Brasil / Instituto Brasileiro para a Investigação da Tuberculose. Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brazil
National Institutes of Health- NIRT. International Center for Excellence in Research. Chennai, India
University of São Paulo. School of Pharmaceutical Sciences. Department of Pathophysiology and Toxicology. São Paulo, SP, Brazil
University of Massachusetts Medical School. Department of Medicine. Worcester, Massachusetts. USA
National Institute for Research in Tuberculosis. Chennai, India
National Institute for Research in Tuberculosis. Chennai, India
Prof. M. Viswanathan Diabetes Research Center. Chennai, India
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação. Unidade de Medicina Investigativa. Salvador, BA, Brasil / Instituto Brasileiro para a Investigação da Tuberculose. Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brazil / Universidade Salvador. Laureate Universities. Salvador, BA, Brazil / Vanderbilt University School of Medicine. Division of Infectious Diseases. Department of Medicine Nashville. USA
University of São Paulo. School of Pharmaceutical Sciences. Department of Pathophysiology and Toxicology. São Paulo, SP, Brazil
University of Massachusetts Medical School. Department of Medicine. Worcester, Massachusetts, USA
Abstract
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.
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