MARIA ELIZABETH ROSSI DA SILVA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina - Líder
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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.- Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G > A variant with type 1 diabetes in a Brazilian cohort(2015) PATENTE, Thiago A.; MONTEIRO, Maria B.; VIEIRA, Suzana M.; SILVA, Maria E. Rossi da; NERY, Marcia; QUEIROZ, Marcia; AZEVEDO, Mirela J.; CANANI, Luis H.; PARISI, Maria C.; PAVIN, Elizabeth J.; MAINARDI, Debora; JAVOR, Juraj; VELHO, Gilberto; COIMBRA, Cassio N.; CORREA-GIANNELLA, Maria LuciaBackground: A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association.. Methods: 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HIA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. Results: Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69,95% Cl 133-2.15, p < 0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% Cl 3.23-8.59, p < 0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% Cl 1.21-7.21, p = 0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14,95% Cl 1.02-4.50, p = 0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. Conclusion: Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D.
- Prevalence of Inflammatory Pathways Over Immuno-Tolerance in Peripheral Blood Mononuclear Cells of Recent-Onset Type 1 Diabetes(2022) SANTOS, Aritania Sousa; CUNHA-NETO, Edecio; GONFINETTI, Nelson Vinicius; BERTONHA, Fernanda Bernardi; BROCHET, Pauline; BERGON, Aurelie; MOREIRA-FILHO, Carlos Alberto; CHEVILLARD, Christophe; SILVA, Maria Elizabeth Rossi daBackgroundChanges in innate and adaptive immunity occurring in/around pancreatic islets had been observed in peripheral blood mononuclear cells (PBMC) of Caucasian T1D patients by some, but not all researchers. The aim of our study was to investigate whether gene expression patterns of PBMC of the highly admixed Brazilian population could add knowledge about T1D pathogenic mechanisms. MethodsWe assessed global gene expression in PBMC from two groups matched for age, sex and BMI: 20 patients with recent-onset T1D (<= 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls. ResultsWe identified 474 differentially expressed genes between groups. The most expressed genes in T1D group favored host defense, inflammatory and anti-bacterial/antiviral effects (LFT, DEFA4, DEFA1, CTSG, KCNMA1) and cell cycle progression. Several of the downregulated genes in T1D target cellular repair, control of inflammation and immune tolerance. They were related to T helper 2 pathway, induction of FOXP3 expression (AREG) and immune tolerance (SMAD6). SMAD6 expression correlated negatively with islet ZnT8 antibody. The expression of PDE12, that offers resistance to viral pathogens was decreased and negatively related to ZnT8A and GADA levels. The increased expression of long non coding RNAs MALAT1 and NEAT1, related to inflammatory mediators, autoimmune diseases and innate immune response against viral infections reinforced these data ConclusionsOur analysis suggested the activation of cell development, anti-infectious and inflammatory pathways, indicating immune activation, whereas immune-regulatory pathways were downregulated in PBMC from recent-onset T1D patients with a differential genetic profile.
- Biomarkers of insulin action during single soccer sessions before and after a 12-week training period in type 2 diabetes patients on a caloric-restricted diet(2019) SOUSA, Maysa V. de; FUKUI, Rosa; DAGOGO-JACK, Samuel; KRUSTRUP, Peter; ZOUHAL, Hassane; SILVA, Maria Elizabeth R. daBackground: We investigated the biomarkers of insulin action as well as changes in free fatty acids and lactate concentration after an acute soccer session pre and post training with caloric-restricted diet versus diet alone in type 2 diabetes (T2D) patients. Methods: Fifty-one middle-aged (61.1 +/- 6.4 years) T2D patients were randomly allocated to the soccer + diet group (SDG) or the diet group (DG). The control group comprised T2D patients observing a caloric-restricted diet who did not receive soccer training. Over 12 weeks, SDG performed 3 x 40 min per week of soccer training. Results: The first soccer session for SDG induced acute increases in blood lactate (1.4 +/- 0.1-6.0 +/- 0.7 mmol/l, P < 0.05) and glucagon levels (112.1 +/- 6.2-142.9 +/- 8.0 pg/ml, P < 0.05), whereas glucose and insulin levels remained unchanged. Moreover, this session showed suppressed insulin levels as well as higher free fatty acids, lactate levels and glucagon/insulin ratio compared to DG (p < 0.05). After 12 weeks, a baseline decrease was observed in glucagon, leptin and lactate levels in SDG and DG (p < 0.05), whereas HOMA-IR, Adipo-IR and glucose levels were lower only in SDG (p < 0.05). At the last soccer training session, the blood lactate response was significantly lower than for the first session (4.0 +/- 0.4 vs 6.0 +/- 0.7 mmol/l). At 48 h pre intervention, a decrease was observed in leptin levels (p < 0.05), which remained lower post intervention. The positive correlation between leptin and insulin, and the lower levels after training, could be attributed to the improved insulin sensitivity along with the weight loss observed in both groups (similar to 3.4 kg for DG and 3.7 kg for SDG). Conclusion: Acute soccer sessions markedly improved insulin action markers in T2D patients, while the cumulative effects enhanced insulin sensitivity and decreased risk factors associated with cardiovascular disease after 12 weeks of intervention better than caloric-restricted diet.