EDECIO CUNHA NETO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina - Líder
37 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 37
- Polymorphism in the Alpha Cardiac Muscle Actin 1 Gene Is Associated to Susceptibility to Chronic Inflammatory Cardiomyopathy(2013) FRADE, Amanda Farage; TEIXEIRA, Priscila Camilo; IANNI, Barbara Maria; PISSETTI, Cristina Wide; SABA, Bruno; WANG, Lin Hui Tzu; KURAMOTO, Andreia; NOGUEIRA, Luciana Gabriel; BUCK, Paula; DIAS, Fabricio; GINIAUX, Helene; LLORED, Agnes; ALVES, Sthefanny; SCHMIDT, Andre; DONADI, Eduardo; MARIN-NETO, Jose Antonio; HIRATA, Mario; SAMPAIO, Marcelo; FRAGATA, Abilio; BOCCHI, Edimar Alcides; STOLF, Antonio Noedir; FIORELLI, Alfredo Inacio; SANTOS, Ronaldo Honorato Barros; RODRIGUES, Virmondes; PEREIRA, Alexandre Costa; KALIL, Jorge; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheAims: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to a life-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infected individuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin (ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1 gene in CCC pathogenesis. Methods and Results: We conducted a proteomic and genetic study on a Brazilian study population. The genetic study was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and the replication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower in myocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping a case-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1 gene identified rs640249 SNP, located at the 5' region, as associated to CCC. Associations are borderline after correction for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype. Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in the promoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replication cohort will be useful. Conclusions: Genetic variations at the ACTC1 gene may contribute to progression to chronic Chagas Cardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1 promoter regions.
- Disease Tolerance and Pathogen Resistance Genes May Underlie Trypanosoma cruzi Persistence and Differential Progression to Chagas Disease Cardiomyopathy(2018) CHEVILLARD, Christophe; NUNES, Joao Paulo Silva; FRADE, Amanda Farage; ALMEIDA, Rafael Ribeiro; PANDEY, Ramendra Pati; NASCIMENTO, Marilda Savoia; KALIL, Jorge; CUNHA-NETO, EdecioChagas disease is caused by infection with the protozoan Trypanosoma cruzi and affects over 8 million people worldwide. In spite of a powerful innate and adaptive immune response in acute infection, the parasite evades eradication, leading to a chronic persistent infection with low parasitism. Chronically infected subjects display differential patterns of disease progression. While 30% develop chronic Chagas disease cardiomyopathy (CCC)-a severe inflammatory dilated cardiomyopathy-decades after infection, 60% of the patients remain disease-free, in the asymptomatic/indeterminate (ASY) form, and 10% develop gastrointestinal disease. Infection of genetically deficient mice provided a map of genes relevant for resistance to T. cruzi infection, leading to the identification of multiple genes linked to survival to infection. These include pathogen resistance genes (PRG) needed for intracellular parasite destruction, and genes involved in disease tolerance (protection against tissue damage and acute phase death-DTG). All identified DTGs were found to directly or indirectly inhibit IFN-gamma production or Th1 differentiation. We hypothesize that the absolute need for DTG to control potentially lethal IFN-gamma PRG activity leads to T. cruzi persistence and establishment of chronic infection. IFN-gamma production is higher in CCC than ASY patients, and is the most highly expressed cytokine in CCC hearts. Key DTGs that downmodulate IFN-gamma, like IL-10, and Ebi3/IL27p28, are higher in ASY patients. Polymorphisms in PRG and DTG are associated with differential disease progression. We thus hypothesize that ASY patients are disease tolerant, while an imbalance of DTG and IFN-gamma PRG activity leads to the inflammatory heart damage of CCC.
conferenceObject Whole exome sequencing of Chagas disease cardiomyopathy families reveals accumulation of rare variants in mitochondrial and inflammation-associated genes(2019) CUNHA-NETO, E.; MARQUET, S.; FRADE, A. Farage; FERREIRA, A. Mota; OUARHACHE, M.; IANNI, B.; FERREIRA, L. Rodrigues Pinto; RIGAUD, V. Oliveira-Carvalho; ALMEIDA, R. Ribeiro; CANDIDO, D.; TORRES, M.; GALLARDO, F.; FERNANDES, R.; MADY, C.; BUCK, P.; CARDOSO, C.; SANTOS-JUNIOR, O. R.; OLIVEIRA, L. C.; OLIVEIRA, C. D. L.; NUNES, M. do Carmo; ABEL, L.; KALIL, J.; RIBEIRO, A. L. P.; SABINO, E. C.; CHEVILLARD, C.conferenceObject Gene expression profile of peripheral blood mononuclear cells of recent-onset type 1 diabetes(2018) SANTOS, A. S.; CHEVILLARD, C.; GONFINETTI, N. V.; KALIL, J.; CUNHA-NETO, E.; SILVA, M. R.- Mitochondria at the Crossroads of Immunity and Inflammatory Tissue Damage(2021) NUNES, Joao Paulo Silva; MORAES-VIEIRA, Pedro M.; CHEVILLARD, Christophe; CUNHA-NETO, Edecio
- Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways(2013) FRADE, Amanda Farage; PISSETTI, Cristina Wide; IANNI, Barbara Maria; SABA, Bruno; LIN-WANG, Hui Tzu; NOGUEIRA, Luciana Gabriel; BORGES, Ariana de Melo; BUCK, Paula; DIAS, Fabricio; BARON, Monique; FERREIRA, Ludmila Rodrigues Pinto; SCHMIDT, Andre; MARIN-NETO, Jose Antonio; HIRATA, Mario; SAMPAIO, Marcelo; FRAGATA, Abilio; PEREIRA, Alexandre Costa; DONADI, Eduardo; KALIL, Jorge; RODRIGUES, Virmondes; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheBackground: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the most important clinical consequence of T. cruzi infection. The others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Migration of Th1-type T cells play a major role in myocardial damage. Methods: Our genetic analysis focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach, defined to catch all the genetic information from each gene. The study was conducted on a large Brazilian population including 315 CCC cases and 118 ASY subjects. Results: The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to protection to CCC. These associations were confirmed when we restricted the analysis to severe CCC, characterized by a left ventricular ejection fraction under 40%. Conclusions: Our data show that polymorphisms affecting key molecules involved in several immune parameters (innate immunity signal transduction and T cell/monocyte migration) play a role in genetic susceptibility to CCC development. This also points out to the multigenic character of CCC, each polymorphism imparting a small contribution. The identification of genetic markers for CCC will provide information for pathogenesis as well as therapeutic targets.
- SBC Guideline on the Diagnosis and Treatment of Patients with Cardiomyopathy of Chagas Disease-2023(2023) MARIN-NETO, Jose Antonio; JR, Anis Rassi; OLIVEIRA, Glaucia Maria Moraes; CORREIA, Luis Claudio Lemos; RAMOS JUNIOR, Alberto Novaes; LUQUETTI, Alejandro Ostermayer; HASSLOCHER-MORENA, Alejandro Marcel; SOUSA, Andrea Silvestre de; PAOLA, Angelo Amato Vincenzo de; SOUSA, Antonio Carlos Sobral; RIBEIRO, Antonio Luiz Pinho; CORREIA FILHO, Dalmo; SOUZA, Dilma do Socorro Moraes de; CUNHA-NETO, Edecio; RAMIRES, Felix Jose Alvarez; BACAL, Fernando; NUNES, Maria do Carmo Pereira; MARTINELLI FILHO, Martino; SCANAVACCA, Maurici Ibrahim; SARAIVA, Roberto Magalhaes; OLIVEIRA JUNIOR, Wilson Alves de; LORGA-FILHO, Adalberto Menezes; GUIMARAES, Adriana de Jesus Benevides de Almeida; BRAGA, Adriana Lopes Latado; OLIVEIRA, Adriana Sarmento de; SARABANDA, Alvaro Valentim Lima; PINTO, Ana Yece das Neves; CARMO, Andre Assis Lopes do; SCHMIDT, Andre; COSTA, Andrea Rodrigues da; IANNI, Barbara Maria; MARKMAN FILHO, Brivaldo; ROCHITT, Carlos Eduardo; MACEDO, Carolina The; MADY, Charles; CHEVILLARD, Christophe; VIRGENS, Claudio Marcelo Bittencourt das; CASTRO, Cleudson Nery de; BRITTO, Constanca Felicia De Paoli de Carvalho; PISANI, Cristiano; RASSI, Daniel do Carmo; SOBRAL FILHO, Dario Celestino; ALMEIDA, Dirceu Rodrigues de; BOCCHI, Edimar Alcides; MESQUITA, Evandro Tinoco; MENDES, Fernanda de Souza Nogueira Sardinha; GONDIM, Francisca Tatiana Pereira; SILVA, Gilberto Marcelo Sperandio da; PEIXOTO, Giselle de Lima; LIMA, Gustavo Glotz de; VELOSO, Henrique Horta; MOREIRA, Henrique Turin; LOPES, Hugo Bellotti; PINTO, Ibraim Masciarelli Francisco; FERREIRA, Joao Marcos Bemfica Barbosa; NUNES, Joao Paulo Silva; BARRETO-FILHO, Jose Augusto Soares; SARAIVA, Jose Francisco Kerr; LANNES-VIEIRA, Joseli; OLIVEIRA, Joselina Luzia Menezes; ARMAGANIJAN, Luciana Vidal; MARTINS, Luiz Claudio; SANGENIS, Luiz Henrique Conde; BARBOSA, Marco Paulo Tomaz; ALMEIDA-SANTOS, Marcos Antonio; SIMOES, Marcos Vinicius; YASUDA, Maria Aparecida Shikanai; MOREIRA, Maria da Consolacao Vieira; HIGUCHI, Maria de Lourdes; MONTEIRO, Maria Rita de Cassia Costa; MEDIANO, Mauro Felippe Felix; LIMA, Mayara Maia; OLIVEIRA, Maykon Tavares de; ROMANO, Minna Moreira Dias; ARAUJO, Nadjar Nitz Silva Lociks de; MEDEIROS, Paulo de Tarso Jorge; ALVES, Renato Vieira; TEIXEIRA, Ricardo Alkmim; PEDROSA, Roberto Coury; ARAS JUNIOR, Roque; TORRES, Rosalia Morais; POVOA, Rui Manoel dos Santos; RASSI, Sergio Gabriel; ALVES, Silvia Marinho Martins; TAVARES, Suelene Brito do Nascimento; PALMEIRA, Swamy Lima; SILVA JUNIOR, Telemaco Luiz da; RODRIGUES, Thiago da Rocha; MADRINI JUNIOR, Vagner; BRANT, Veruska Maia da Costa; DUTRA, Walderez Ornelas; DIAS, Joao Carlos Pinto
- Chagas Disease Cardiomyopathy: Immunopathology and Genetics(2014) CUNHA-NETO, Edecio; CHEVILLARD, ChristopheChagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects ca. 10 million people worldwide. About 30% of Chagas disease patients develop chronic Chagas disease cardiomyopathy (CCC), a particularly lethal inflammatory cardiomyopathy that occurs decades after the initial infection, while most patients remain asymptomatic. Mortality rate is higher than that of noninflammatory cardiomyopathy. CCC heart lesions present a Th1 T-cell-rich myocarditis, with cardiomyocyte hypertrophy and prominent fibrosis. Data suggest that the myocarditis plays a major pathogenetic role in disease progression. Major unmet goals include the thorough understanding of disease pathogenesis and therapeutic targets and identification of prognostic genetic factors. Chagas disease thus remains a neglected disease, with no vaccines or antiparasitic drugs proven efficient in chronically infected adults, when most patients are diagnosed. Both familial aggregation of CCC cases and the fact that only 30% of infected patients develop CCC suggest there might be a genetic component to disease susceptibility. Moreover, previous case-control studies have identified some genes associated to human susceptibility to CCC. In this paper, we will review the immunopathogenesis and genetics of Chagas disease, highlighting studies that shed light on the differential progression of Chagas disease patients to CCC.
- The oldest unvaccinated Covid-19 survivors in South America(2022) V, Mateus de Castro; SILVA, Monize V. R.; NASLAVSKY, Michel S.; SCLIAR, Marilia O.; NUNES, Kelly; PASSOS-BUENO, Maria Rita; CASTELLI, Erick C.; MAGAWA, Jhosiene Y.; ADAMI, Flavia L.; MORETTI, Ana I. S.; OLIVEIRA, Vivian L. de; BOSCARDIN, Silvia B.; CUNHA-NETO, Edecio; KALIL, Jorge; JOUANGUY, Emmanuelle; BASTARD, Paul; CASANOVA, Jean-Laurent; QUINONES-VEGA, Mauricio; SOSA-ACOSTA, Patricia; GUEDES, Jessica S. de; ALMEIDA, Natalia P. de; NOGUEIRA, Fabio C. S.; DOMONT, Gilberto B.; SANTOS, Keity S.; ZATZ, MayanaBackground Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. Results Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. Conclusion These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.
- Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease(2021) OUARHACHE, Maryem; MARQUET, Sandrine; FRADE, Amanda Farage; FERREIRA, Ariela Mota; IANNI, Barbara; ALMEIDA, Rafael Ribeiro; NUNES, Joao Paulo Silva; FERREIRA, Ludmila Rodrigues Pinto; RIGAUD, Vagner Oliveira-Carvalho; CANDIDO, Darlan; MADY, Charles; ZANIRATTO, Ricardo Costa Fernandes; BUCK, Paula; TORRES, Magali; GALLARDO, Frederic; ANDRIEUX, Pauline; BYDLOWSKY, Sergio; LEVY, Debora; ABEL, Laurent; CARDOSO, Clareci Silva; SANTOS-JUNIOR, Omar Ribeiro; OLIVEIRA, Lea Campos; OLIVEIRA, Claudia Di Lorenzo; NUNES, Maria Do Carmo; COBAT, Aurelie; KALIL, Jorge; RIBEIRO, Antonio Luiz; SABINO, Ester Cerdeira; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheCardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)). The cytokine interferon-gamma and mitochondrial dysfunction are known to play a major pathogenetic role. Chagas disease provides a unique model to probe for genetic variants involved in inflammatory cardiomyopathy. Methods We used whole exome sequencing to study nuclear families containing multiple cases of Chagas disease. We searched for rare pathogenic variants shared by all family members with CCC but absent in infected ASY siblings and in unrelated ASY. Results We identified heterozygous, pathogenic variants linked to CCC in all tested families on 22 distinct genes, from which 20 were mitochondrial or inflammation-related - most of the latter involved in proinflammatory cytokine production. Significantly, incubation with IFN-gamma on a human cardiomyocyte line treated with an inhibitor of dihydroorotate dehydrogenase brequinar (enzyme showing a loss-of-function variant in one family) markedly reduced mitochondrial membrane potential (Delta psi M), indicating mitochondrial dysfunction. Conclusion Mitochondrial dysfunction and inflammation may be genetically determined in CCC, driven by rare genetic variants. We hypothesize that CCC-linked genetic variants increase mitochondrial susceptibility to IFN-gamma-induced damage in the myocardium, leading to the cardiomyopathy phenotype in Chagas disease. This mechanism may also be operative in other inflammatory cardiomyopathies.