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https://www.arca.fiocruz.br/handle/icict/34556
MOLECULAR DEGREE OF PERTURBATION OF PLASMA INFLAMMATORY MARKERS ASSOCIATED WITH TUBERCULOSIS REVEALS DISTINCT DISEASE PROFILES BETWEEN INDIAN AND CHINESE POPULATIONS
Author
Souza, Deivide Oliveira de
Vinhaes, Caian L.
Arriaga Gutiérrez, María Belen
Kumar, Nathella Pavan
Angulo, Juan M Cubillos
Shi, Ruiru
Wei, Wang
Yuan, Xing
Zhang, Guolong
Cai, Ying
Barry, Clifton E.
Via, Laura E.
Sher, Alan
Babu, Subash
Barber, Katrin D. Mayer
Nakaya, Helder I.
Fukutani, Kiyoshi Ferreira
Andrade, Bruno de Bezerril
Vinhaes, Caian L.
Arriaga Gutiérrez, María Belen
Kumar, Nathella Pavan
Angulo, Juan M Cubillos
Shi, Ruiru
Wei, Wang
Yuan, Xing
Zhang, Guolong
Cai, Ying
Barry, Clifton E.
Via, Laura E.
Sher, Alan
Babu, Subash
Barber, Katrin D. Mayer
Nakaya, Helder I.
Fukutani, Kiyoshi Ferreira
Andrade, Bruno de Bezerril
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
National Institutes of Health. National Institute for Research in Tuberculosis. International Center for Excellence in Research. India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
Henan Chest Hospital. Zhengzhou, China.
Henan Chest Hospital. Zhengzhou, China.
Henan Chest Hospital. Zhengzhou, China.
Sino-US International Research Center for Tuberculosis. Henan Public Health Center. Zhengzhou, China.
Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.
Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.
Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.
Laboratory of Parasitic Diseases. Bethesda, USA.
National Institutes of Health. National Institute for Research in Tuberculosis. International Center for Excellence in Research. India.
Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.
University of São Paulo. School of Pharmaceutical Sciences. Department of Pathophysiology and Toxicology. São Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Division of Infectious Diseases. Department of Medicine. USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
National Institutes of Health. National Institute for Research in Tuberculosis. International Center for Excellence in Research. India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
Henan Chest Hospital. Zhengzhou, China.
Henan Chest Hospital. Zhengzhou, China.
Henan Chest Hospital. Zhengzhou, China.
Sino-US International Research Center for Tuberculosis. Henan Public Health Center. Zhengzhou, China.
Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.
Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.
Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.
Laboratory of Parasitic Diseases. Bethesda, USA.
National Institutes of Health. National Institute for Research in Tuberculosis. International Center for Excellence in Research. India.
Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.
University of São Paulo. School of Pharmaceutical Sciences. Department of Pathophysiology and Toxicology. São Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Division of Infectious Diseases. Department of Medicine. USA.
Abstract
Tuberculosis (TB) is a chronic inflammatory disease caused by Mycobacterium tuberculosis infection which causes tremendous morbidity and mortality worldwide. Clinical presentation of TB patients is very diverse and disease heterogeneity is associated with changes in biomarker signatures. Here, we compared at the molecular level the extent of individual inflammatory perturbation of plasma protein and lipid mediators associated with TB in patients in China versus India. We performed a cross-sectional study analyzing the overall degree of inflammatory perturbation in treatment-naïve pulmonary TB patients and uninfected individuals from India (TB: n = 97, healthy: n = 20) and China (TB: n = 100, healthy: n = 11). We employed the molecular degree of perturbation (MDP) adapted to plasma biomarkers to examine the overall changes in inflammation between these countries. M. tuberculosis infection caused a significant degree of molecular perturbation in patients from both countries, with higher perturbation detected in India. Interestingly, there were differences in biomarker perturbation patterns and the overall degree of inflammation. Patients with severe TB exhibited increased MDP values and Indian patients with this condition exhibited even higher degree of perturbation compared to Chinese patients. Network analyses identified IFN-α, IFN-β, IL-1RI and TNF-α as combined biomarkers that account for the overall molecular perturbation in the entire study population. Our results delineate the magnitude of the systemic inflammatory perturbation in pulmonary TB and reveal qualitative changes in inflammatory profiles between two countries with high disease prevalence.
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