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https://www.arca.fiocruz.br/handle/icict/53421
SYSTEMIC CYTOKINES, CHEMOKINES AND GROWTH FACTORS REVEAL SPECIFIC AND SHARED IMMUNOLOGICAL CHARACTERISTICS IN INFECTIOUS CARDIOMYOPATHIES
Author
Neves, Eula Graciele Amorim
Koh, Carolina Cattoni
Silva, José L Padilha da
Passos, Livia Silva Araújo
Villani, Fernanda Nobre Amaral
Santos, Janete Soares Coelho dos
Menezes, Cristiane Alves da Silva
Silva, Vicente R
Tormin, Julia P A S
Evangelista, Guilherme F B
Carvalho, Andréa Teixeira de
Rocha, Manoel Otávio da Costa
Nascimento, Bruno
Gollob, Kenneth John
Nunes, Maria do Carmo P
Dutra, Walderez Ornelas
Koh, Carolina Cattoni
Silva, José L Padilha da
Passos, Livia Silva Araújo
Villani, Fernanda Nobre Amaral
Santos, Janete Soares Coelho dos
Menezes, Cristiane Alves da Silva
Silva, Vicente R
Tormin, Julia P A S
Evangelista, Guilherme F B
Carvalho, Andréa Teixeira de
Rocha, Manoel Otávio da Costa
Nascimento, Bruno
Gollob, Kenneth John
Nunes, Maria do Carmo P
Dutra, Walderez Ornelas
Affilliation
Statistics Department. Federal University of Paraná. Curitiba, PR, Brazil.
Statistics Department. Federal University of Paraná. Curitiba, PR, Brazil.
Statistics Department. Federal University of Paraná. Curitiba, PR, Brazil.
Cell-cell Interactions Laboratory. Department of Morphology. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Brigham and Women's Hospital. Harvard Medical School. Boston, MA, USA.
Minas Gerais State University. Divinópolis, MG, Brazil.
Ezequiel Dias Foundation. Minas Gerais Estate. Belo Horizonte, MG, Brazil.
Department of Clinical and Toxicological Analysis. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Graduate Program in Infectology and Tropical Medicine. School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Graduate Program in Infectology and Tropical Medicine. School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Hospital Israelita Albert Einstein. São Paulo, SP, Brazil.
Rene Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Graduate Program in Infectology and Tropical Medicine. School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Graduate Program in Infectology and Tropical Medicine. School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Hospital Israelita Albert Einstein. São Paulo, SP, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brazil.
Graduate Program in Infectology and Tropical Medicine. School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Cell-cell Interactions Laboratory. Department of Morphology. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brazil
Statistics Department. Federal University of Paraná. Curitiba, PR, Brazil.
Statistics Department. Federal University of Paraná. Curitiba, PR, Brazil.
Cell-cell Interactions Laboratory. Department of Morphology. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Brigham and Women's Hospital. Harvard Medical School. Boston, MA, USA.
Minas Gerais State University. Divinópolis, MG, Brazil.
Ezequiel Dias Foundation. Minas Gerais Estate. Belo Horizonte, MG, Brazil.
Department of Clinical and Toxicological Analysis. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Graduate Program in Infectology and Tropical Medicine. School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Graduate Program in Infectology and Tropical Medicine. School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Hospital Israelita Albert Einstein. São Paulo, SP, Brazil.
Rene Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Graduate Program in Infectology and Tropical Medicine. School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Graduate Program in Infectology and Tropical Medicine. School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Hospital Israelita Albert Einstein. São Paulo, SP, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brazil.
Graduate Program in Infectology and Tropical Medicine. School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Cell-cell Interactions Laboratory. Department of Morphology. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brazil
Abstract
Heart disease is a major cause of death worldwide. Chronic Chagas cardiomyopathy (CCC) caused by infection with Trypanosoma cruzi leading to high mortality in adults, and rheumatic heart disease (RHD), resulting from infection by Streptococcus pyogenes affecting mainly children and young adults, are amongst the deadliest heart diseases in low-middle income countries. Despite distinct etiology, the pathology associated with both diseases is a consequence of inflammation. Here we compare systemic immune profile in patients with these cardiopathies, to identify particular and common characteristics in these infectious heart diseases. We evaluated the expression of 27 soluble factors, employing single and multivariate analysis combined with machine-learning approaches. We observed that, while RHD and CCC display higher levels of circulating mediators than healthy individuals, CCC is associated with stronger immune activation as compared to RHD. Despite distinct etiologies, univariate analysis showed that expression of TNF, IL-17, IFN-gamma, IL-4, CCL4, CCL3, CXCL8, CCL11, CCL2, PDGF-BB were similar between CCC and RHD, consistent with their inflammatory nature. Network analysis revealed common inflammatory pathways between CCC and RHD, while highlighting the broader reach of the inflammatory response in CCC. The final multivariate model showed a 100% discrimination power for the combination of the cytokines IL-12p70, IL-1Ra, IL-4, and IL-7 between CCC and RHD groups. Thus, while clear immunological distinctions were identified between CCC and RHD, similarities indicate shared inflammatory pathways in these infectious heart diseases. These results contribute to understanding the pathogenesis of CCC and RHD and may impact the design of immune-based therapies for these and other inflammatory cardiopathies that may also share immunological characteristics.
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