FERNANDA DE TOLEDO GONCALVES
Projetos de Pesquisa
Unidades Organizacionais
LIM/40 - Laboratório de Imunohematologia e Hematologia Forense, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
Agora exibindo 1 - 3 de 3
- Casework direct kit as an alternative extraction method to enhance touch DNA samples analysis(2020) FRANCISCO, Daniela de Oliveira; LOPEZ, Luis Fernandez; GONCALVES, Fernanda de Toledo; FRIDMAN, Cintia
- 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.
- Systemic cytokines and GlycA discriminate disease status and predict corticosteroid response in HTLV-1-associated neuroinflammation(2022) ASSONE, Tatiane; MENEZES, Soraya Maria; GONCALVES, Fernanda de Toledo; FOLGOSI, Victor Angelo; PRATES, Gabriela da Silva; DIERCKX, Tim; BRAZ, Marcos; SMID, Jerusa; HAZIOT, Michel E.; MARCUSSO, Rosa M. N.; DAHY, Flavia E.; VANDERLINDEN, Evelien; CLAES, Sandra; SCHOLS, Dominique; BRUHN, Roberta; MURPHY, Edward L.; OLIVEIRA, Augusto Cesar Penalva de; DAELEMANS, Dirk; VERCAUTEREN, Jurgen; CASSEB, Jorge; WEYENBERGH, Johan VanBackground: HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors. Patients and methods: We recruited 110 People living with HTLV-1 (PLHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients) with a total of 946 person-years of clinical follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-gamma, TNF) and GlycA were quantified by Cytometric Bead Array and (NMR)-N-1, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We used multivariable regression, machine learning algorithms and Bayesian network learning for biomarker identification. Results: We found that systemic IL-6 was positively correlated with both age (r = 0.50, p < 0.001) and GlycA (r = 0.45, p = 0.00049) in asymptomatics, revealing an 'inflammaging "" signature which was absent in HAM/TSP. GlycA levels were higher in women (p = 0.0069), but cytokine levels did not differ between the sexes. IFN-gamma (p = 0.007) and IL-17A (p = 0.0001) levels were increased in untreated HAM/TSP Multivariable logistic regression identified IL-17A and proviral load as independent determinants of clinical status, resulting in modest accuracy of predicting HAM/TSP status (64.1%), while a machine learning-derived decision tree classified HAM/TSP patients with 90.7% accuracy. Pre-treatment GlycA and TNF levels significantly predicted clinical worsening (measured by Osame Motor Disability Scale), independent of proviral load. In addition, a poor prednisolone response was significantly correlated with higher post-treatment IFN-gamma levels. Likewise, a transcriptomic IFN signaling score, significantly correlated with previously proposed HAM/TSP biomarkers (CASP5/CXCL10/FCGR1A/STAT1), was efficiently blunted by in vitro prednisolone treatment of PBMC from PLHTLV-1 and incident HAM/TSP. Conclusions: An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLHTLV-1, in the absence of neurological disease. IFN-gamma and IL-17A are biomarkers of untreated HAM/TSP, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy, paving the way for a precision medicine approach in HAM/TSP.