FERNANDA DE TOLEDO GONCALVES
Projetos de Pesquisa
Unidades Organizacionais
LIM/40 - Laboratório de Imunohematologia e Hematologia Forense, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- AIDS incidence and survival in a hospital-based cohort of HIV-positive patients from Sao Paulo, Brazil: The role of IFN-lambda 4 polymorphisms(2021) PRATES, Gabriela da Silva; MALTA, Fernanda M.; GONCALVES, Fernanda de Toledo; MONTEIRO, Mariana A.; FONSECA, Luiz Augusto M.; VEIGA, Ana Paula R.; MAGRI, Marcello M. C.; DUARTE, Alberto J. S.; CASSEB, Jorge; ASSONE, TatianeFew studies have reported the prognosis of human immunodeficiency virus (HIV)-positive patients followed for a long time in Brazil, particularly those including pre and post-HAART eras. The polymorphisms of interferon (IFN)-lambda 4 have been postulated as possibly associated with the pathogenesis of HIV infection. The aim of this study was to describe the incidence and mortality from a cohort of HIV-positive patients as well as whether IFN-lambda 4 gene polymorphisms (SNP rs8099917 and SNP rs12979860) were associated with HIV/acquired immune deficiency syndrome (AIDS) progression. We followed 402 patients for up to 30 years; 347 of them began follow-up asymptomatic, without any AIDS-defining opportunistic disease and/or a lymphocytes T CD4+ count of 350 cells/mm(3)or lower. We determined the probability of the asymptomatic subjects to remain AIDS-free, and the risk of death for those entering the study already with an AIDS diagnosis, as well as for subjects developing AIDS during follow-up. We compared the prognosis of patients with two different polymorphisms for the genes encoding for IFN-lambda 4, variants rs8099917 and rs12979860. The follow-up time of the 347 asymptomatic-at-entry subjects was 3687 person-years. IFN-lambda 4 rs8099917 polymorphisms were not associated with AIDS progression, but IFN-lambda 4 rs12979860 wild type genotype (CC) was associated with higher mortality compared to CT and TT, with an increased probability of death from AIDS (P = .01). In conclusion, genetic variations in IFN-lambda 4 on rs12979860 polymorphisms in HIV-infected patients may drive mortality risk.
- Polymorphisms in HLA-C and KIR alleles are not associated with HAM/TSP risk in HTLV-1-infected subjects(2018) ASSONE, Tatiane; MALTA, Fernanda M.; BAKKOUR, Sonia; MONTALVO, Leilani; PAIVA, Arthur M.; SMID, Jerusa; OLIVEIRA, Augusto Cesar Penalva de; GONCALVES, Fernanda de Toledo; LUIZ, Olinda do Carmo; FONSECA, Luiz Augusto M.; NORRIS, Philip J.; CASSEB, JorgeIntroduction: Several genetic polymorphisms may be related to susceptibility or resistance to viral disease outcomes. Immunological or genetic factors may act as major triggers of the immune pathogenesis of HAM/TSP. This study investigated the association of immune related genetic polymorphisms with viral and immunological markers. Methods: 247 HTLV-1-infected volunteers, drawn from a larger group of HTLV-infected subjects followed at the Institute of Infectious Diseases ""Emilio Ribas"" (IIER) for up to 19 years, participated in this study, which ran from June 2011 to July 2016. The subjects were classified according to their neurological status into two groups: Group 1 (160 asymptomatic individuals) and Group 2 (87 HAM/TSP patients). Samples were tested for spontaneous lymphocyte proliferation (LPA) and HTLV-1 proviral load (PVL) and for IFN-lambda 4, HLA-C and KIR genotypes using qPCR. Results: We found associations between LPA (p = 0.0001) with HAM/TSP and confirmed the IFN-lambda 4 polymorphism rs8099917, allele GG, as a protective factor using a recessive model (OR = 3.22, CI = 1.10-9.47). Polymorphisms in HLA-C and KIR alleles were not associated with risk of developing HAM/TSP. Conclusion: We demonstrated that age, LPA and an IFN-lambda 4 polymorphism were associated with progression to HAM/TSP. Understanding HAM/TSP pathogenesis can provide important markers of prognostic value for clinical management, and contribute to the discovery of new therapeutic interventions in the future.
- Prognosis Markers for Monitoring HTLV-1 Neurologic Disease(2021) PRATES, Gabriela; ASSONE, Tatiane; CORRAL, Marcelo; BALDASSIN, Maira P. M.; MITIKO, Tatiane; SALES, Flavia C. Silva; HAZIOT, Michel E.; SMID, Jerusa; FONSECA, Luiz A. M.; GONCALVES, Fernanda de Toledo; OLIVEIRA, Augusto C. Penalva de; CASSEB, JorgeBackground Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated not only with some severe manifestations, such as HTLV-1-associated myelopathy (HAM) and ATLL, but also with other, less severe conditions. Some studies have reported neurologic manifestations that did not meet all the criteria for the diagnosis of HAM in individuals infected with HTLV-1; these conditions may later progress to HAM or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. This study evaluated the prognostic value and looked for a possible association of those parameters with the intermediate syndrome (IS) status and HAM status. Methods Proviral load (PVL), spontaneous lymphoproliferation, interferon (IFN)-gamma spontaneous production was quantified in samples of asymptomatic and HAM patients, as well as patients with IS. Results The critical age range was 50-60 years for IS outcome and more of 60 years for HAM outcome, with an increased risk of 2.5-fold for IS and 6.8-fold for HAM. IFN-gamma was increased in patients with IS compared with asymptomatic carriers (ACs) (p = 0.007) and in patients with HAM compared with ACs (p = 0.03). Lymphoproliferation was increased in patients with HAM vs ACs (p = 0.0001) and patients with IS (p = 0.0001). PVL was similar between groups. Conclusion IFN-gamma has high specificity of prediction of subject remain asymptomatic compared with PVL and lymphoproliferation assay tests. IFN-gamma has been shown to be a biomarker of progression to intermediate stage and to HAM. The association of other markers with manifestations associated with HTLV-1 infection that does not meet the HAM criteria should be verified.
- IL28B Gene Polymorphism SNP rs8099917 Genotype GG Is Associated with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in HTLV-1 Carriers(2014) ASSONE, Tatiane; SOUZA, Fernando Vieira de; GAESTER, Karen Oliveira; FONSECA, Luiz Augusto Marcondes; LUIZ, Olinda do Carmo; MALTA, Fernanda; PINHO, Joao Renato Rebello; GONCALVES, Fernanda de Toledo; DUARTE, Alberto Jose da Silva; OLIVEIRA, Augusto Cesar Penalva de; CASSEB, JorgeBackground: The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. Methods: The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. Results: A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95% = 1.82-31.72). Conclusion: Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.