title: Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction.
abstract: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 7 million people in Latin American areas of endemicity. About 30% of infected patients will develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. Further studies are necessary to understand the molecular mechanisms of disease progression. Transcriptome analysis has been increasingly used to identify molecular changes associated with disease outcomes. We thus assessed the whole-blood transcriptome of patients with Chagas disease. Microarray analysis was performed on blood samples from 150 subjects, of whom 30 were uninfected control patients and 120 had Chagas disease (1 group had asymptomatic disease, and 2 groups had CCC with either a preserved or reduced left ventricular ejection fraction [LVEF]). Each Chagas disease group displayed distinct gene expression and functional pathway profiles. The most different expression patterns were between CCC groups with a preserved or reduced LVEF. A more stringent analysis indicated that 27 differentially expressed genes, particularly those related to natural killer (NK)/CD8+ T-cell cytotoxicity, separated the 2 groups. NK/CD8+ T-cell cytotoxicity could play a role in determining Chagas disease progression. Understanding genes associated with disease may lead to improved insight into CCC pathogenesis and the identification of prognostic factors for CCC progression.
authors.affiliation: Laboratory of Immunology and.|Division of Clinical Immunology and Allergy, School of Medicine.|Institute for Investigation in Immunology, National Institute of Science and Technology, and.|Universidade Santo Amaro, São Paulo, and.
authors.forename: Ludmila Rodrigues Pinto
authors.initials: LR
authors.lastname: Ferreira
authors.affiliation: Laboratory of Immunology and.|Division of Clinical Immunology and Allergy, School of Medicine.|Institute for Investigation in Immunology, National Institute of Science and Technology, and.|Universidade Santo Amaro, São Paulo, and.
authors.forename: Frederico Moraes
authors.initials: FM
authors.lastname: Ferreira
authors.affiliation: Department of Pathophysiology and Toxicology, School of Pharmaceutical Sciences, and.|Department of Pathology, Emory University School of Medicine, Atlanta, Georgia; and.
authors.forename: Helder Imoto
authors.initials: HI
authors.lastname: Nakaya
authors.affiliation: Blood Systems Research Institute and.|Department of Laboratory Medicine and.
authors.forename: Xutao
authors.initials: X
authors.lastname: Deng
authors.affiliation: Laboratory of Immunology and.|Division of Clinical Immunology and Allergy, School of Medicine.|Institute for Investigation in Immunology, National Institute of Science and Technology, and.
authors.forename: Darlan da Silva
authors.initials: DD
authors.lastname: Cândido
authors.affiliation: Institute of Tropical Medicine, Department of Infectious Disease, University of São Paulo.
authors.forename: Lea Campos
authors.initials: LC
authors.lastname: de Oliveira
authors.affiliation: Department of Bioinformatics, Qiagen, Redwood City, California.
authors.forename: Jean-Noel
authors.initials: JN
authors.lastname: Billaud
authors.affiliation: Blood Systems Research Institute and.|Institute for Human Genetics, Department of Laboratory Medicine, University of California, San Francisco, and.
authors.forename: Marion C
authors.initials: MC
authors.lastname: Lanteri
authors.affiliation: Laboratory of Immunology and.|Division of Clinical Immunology and Allergy, School of Medicine.|Institute for Investigation in Immunology, National Institute of Science and Technology, and.
authors.forename: Vagner Oliveira-Carvalho
authors.initials: VO
authors.lastname: Rigaud
authors.affiliation: Blood Systems Research Institute and.|Institute for Human Genetics, Department of Laboratory Medicine, University of California, San Francisco, and.
authors.forename: Mark
authors.initials: M
authors.lastname: Seielstad
authors.affiliation: Laboratory of Immunology and.|Division of Clinical Immunology and Allergy, School of Medicine.|Institute for Investigation in Immunology, National Institute of Science and Technology, and.
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.affiliation: Cardiomyopathy Unit, Heart Institute, and.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fernandes
authors.affiliation: Hospital das Clínicas and.|Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: Antonio Luiz P
authors.initials: AL
authors.lastname: Ribeiro
authors.affiliation: Institute of Tropical Medicine, Department of Infectious Disease, University of São Paulo.
authors.forename: Ester Cerdeira
authors.initials: EC
authors.lastname: Sabino
authors.affiliation: Laboratory of Immunology and.|Division of Clinical Immunology and Allergy, School of Medicine.|Institute for Investigation in Immunology, National Institute of Science and Technology, and.
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D046228:Microarray Analysis; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D018754:Ventricular Dysfunction / Q000097:blood / Q000235:genetics* / Q000469:parasitology
keywords: Cardiomyopathy; Chagas disease; NK cells.; whole-blood transcriptome