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
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- 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.
conferenceObject HIV CD4 Based Vaccine Increases CD8 T Cell Responses and Confers Protection Against Challenge with Recombinant Vaccinia Encoding HIV Gag-Pol Proteins(2013) RIBEIRO, S. P.; ROSA, D. S.; KALIL, J.; CUNHA-NETO, E.- Proteins differentially expressed in human beta-cells-enriched pancreatic islet cultures and human insulinomas(2013) TERRA, Leticia F.; TEIXEIRA, Priscila C.; WAILEMANN, Rosangela A. M.; ZELANIS, Andre; PALMISANO, Giuseppe; CUNHA-NETO, Edecio; KALIL, Jorge; LARSEN, Martin R.; LABRIOLA, Leticia; SOGAYAR, Mari C.In view of the great demand for human beta-cells for physiological and medical studies, we generated cell lines derived from human insulinomas which secrete insulin, C-peptide and express neuroendocrine and islet markers. In this study, we set out to characterize their proteomes, comparing them to those of primary beta-cells using DIGE followed by MS. The results were validated by Western blotting. An average of 1800 spots was detected with less than 1% exhibiting differential abundance. Proteins more abundant in human islets, such as Caldesmon, are involved in the regulation of cell contractility, adhesion dependent signaling, and cytoskeletal organization. In contrast, almost all proteins more abundant in insulinoma cells, such as MAGE2, were first described here and could be related to cell survival and resistance to chemotherapy. Our proteomic data provides, for the first time, a molecular snapshot of the orchestrated changes in expression of proteins involved in key processes which could be correlated with the altered phenotype of human beta-cells. Collectively our observations prompt research towards the establishment of bioengineered human beta-cells providing a new and needed source of cultured human beta-cells for beta-cell researeh, along with the development of new therapeutic strategies for detection, characterization and treatment of insulinomas.
- CXCL9/Mig Mediates T cells Recruitment to Valvular Tissue Lesions of Chronic Rheumatic Heart Disease Patients(2013) FAE, Kellen C.; PALACIOS, Selma A.; NOGUEIRA, Luciana G.; OSHIRO, Sandra E.; DEMARCHI, Lea M. F.; BILATE, Angelina M. B.; POMERANTZEFF, Pablo M. A.; BRANDAO, Carlos; THOMAZ, Petronio G.; REIS, Maxwell dos; SAMPAIO, Roney; TANAKA, Ana C.; CUNHA-NETO, Edecio; KALIL, Jorge; GUILHERME, LuizaRheumatic fever (RF) is an autoimmune disease triggered by Streptococcus pyogenes infection frequently observed in infants from developing countries. Rheumatic heart disease (RHD), the major sequel of RF, leads to chronic inflammation of the myocardium and valvular tissue. T cells are the main population infiltrating cardiac lesions; however, the chemokines that orchestrate their recruitment are not clearly defined. Here, we investigated the expression of chemokines and chemokine receptors in cardiac tissue biopsies obtained from chronic RHD patients. Our results showed that CCL3/MIP1 alpha gene expression was upregulated in myocardium while CCL1/I-309 and CXCL9/Mig were highly expressed in valvular tissue. Auto-reactive T cells that infiltrate valvular lesions presented a memory phenotype (CD4(+)CD45RO(+)) and migrate mainly toward CXCL9/Mig gradient. Collectively, our results show that a diverse milieu of chemokines is expressed in myocardium and valvular tissue lesions and emphasize the role of CXCL9/Mig in mediating T cell recruitment to the site of inflammation in the heart.
- 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.
conferenceObject Rest myocardial perfusion disturbance is related to inflammation but not to fibrosis inexperimental chronic chagas cardiomyopathy(2013) OLIVEIRA, L. F. L.; CARVALHO, E. E. V.; MEJIA, J.; SANTANA-SILVA, J.; ROMANNO, M. M. D.; CUNHA-NETO, E.; HIGUCHI, M. L.; MACIEL, B. C.; MARIN-NETO, J. A.; SIMOES, M. V.conferenceObject Antigen Design to Maximize Anti-HIV CD4+T Cell Responses: Provision of Cognate Help, Increased Coverage and Coping with HIV Genetic Variability(2013) CUNHA-NETO, E.; ROSA, D. S.; RIBEIRO, S.; ALMEIDA, R. R.; SANTANA, V. C.; KALIL, J.conferenceObject Broad and Cross-clade CD4+T-Cell Responses Elicited by a DNA Vaccine Encoding Highly Conserved and Promiscuous HIV-1 M-Group Consensus Peptides(2013) ALMEIDA, R. R.; ROSA, D. S.; RIBEIRO, S. P.; SANTANA, V. C.; KALLAS, E. G.; SIDNEY, J.; SETTE, A.; KALIL, J.; CUNHA-NETO, E.conferenceObject Identification of human endogenous retrovirus (HERV-K (HML-2))-specific mucosal CD4+T cell responses in HIV-1-exposed, seronegative individuals(2013) SENGUPTA, Devi; RIBEIRO, Susan; MICHAUD, Henri-Alexandre; LOH, Liyen; TANDON, Ravi; JONES, R.; GARRISON, Keith; YORK, Vanessa; CUNHA-NETO, Edecio; OSTROWSKI, Mario; PILCHER, Christopher; HECHT, Frederick; MARTIN, Jeff; DEEKS, Steven; HUNT, Peter; NIXON, DouglasThe transcriptional silence of human endogenous retroviruses (HERV) can be disrupted in HIV-1 infection. We have reported that the strength of the HERV-specific CD8+ T cell response predicts lower HIV-1 viral load in untreated adults. To determine whether HERV-K immunity plays a role in inhibiting HIV-1 replication at a major site of transmission and CD4+ T cell depletion, we assessed these responses in gut-associated lymphoid tissue (GALT) from rectosigmoid biopsies and blood of HIV-1 exposed, seronegative (HESN) individuals (n=6) by flow cytometry. CMV pp65- and HIV-1 Gag-specific T cells were also measured, and all responses were compared with peripheral antigen-specific responses in uninfected, low-risk controls (n=11). With the exception of stronger CMV-specific CD8+ T cell responses in the HESN group (p=0.024), there were no significant differences between the magnitudes of peripheral antigen-specific T cell responses in the HESN vs. controls. However, HESN subjects had remarkably robust mucosal HIV-1- (median %CD4+cytokine+cells=2.67) and HERV-specific (median %CD4+cytokine+cells=3.41) CD4+ responses, which were much stronger than the corresponding PBMC responses (p=0.0079 and p<0.0001, respectively). These findings suggest that the GALT is an important site of HERV-K expression and immunity in individuals exposed to HIV-1, and should be further investigated in the context of novel vaccine strategies that target conserved antigens such as HERV.- Genome Wide Association Study (GWAS) of Chagas Cardiomyopathy in Trypanosoma cruzi Seropositive Subjects(2013) DENG, Xutao; SABINO, Ester C.; CUNHA-NETO, Edecio; RIBEIRO, Antonio L.; IANNI, Barbara; MADY, Charles; BUSCH, Michael P.; SEISLSTEAD, MarkBackground: Familial aggregation of Chagas cardiac disease in T. cruzi-infected persons suggests that human genetic variation may be an important determinant of disease progression. Objective: To perform a GWAS using a well-characterized cohort to detect single nucleotide polymorphisms (SNPs) and genes associated with cardiac outcomes. Methods: A retrospective cohort study was developed by the NHLBI REDS-II program in Brazil. Samples were collected from 499 T. cruzi seropositive blood donors who had donated between 1996 and 2002, and 101 patients with clinically diagnosed Chagas cardiomyopathy. In 2008-2010, all subjects underwent a complete medical examination. After genotype calling, quality control filtering with exclusion of 20 cases, and imputation of 1,000 genomes variants; association analysis was performed for 7 cardiac and parasite related traits, adjusting for population stratification. Results: The cohort showed a wide range of African, European, and modest Native American admixture proportions, consistent with the recent history of Brazil. No SNPs were found to be highly (P<10(-8)) associated with cardiomyopathy. The two mostly highly associated SNPs for cardiomyopathy (rs4149018 and rs12582717; P-values <10(-6)) are located on Chromosome 12p12.2 in the SLCO1B1 gene, a solute carrier family member. We identified 44 additional genic SNPs associated with six traits at P-value <10(-6) : Ejection Fraction, PR, QRS, QT intervals, antibody levels by EIA, and parasitemia by PCR. Conclusion: This GWAS identified suggestive SNPs that may impact the risk of progression to cardiomyopathy. Although this Chagas cohort is the largest examined by GWAS to date, (580 subjects), moderate sample size may explain in part the limited number of significant SNP variants. Enlarging the current sample through expanded cohorts and meta-analyses, and targeted studies of candidate genes, will be required to confirm and extend the results reported here. Future studies should also include exposed seronegative controls to investigate genetic associations with susceptibility or resitance to T. cruzi infection and non-Chagas cardiomathy.