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
20 resultados
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conferenceObject Evaluation of the Profile of Circulating microRNAs in Individuals with Recent Type 1 Diabetes and Healthy Controls(2017) SANTOS, Aritania S.; FERREIRA, Ludmila R.; FUKUI, Rosa T.; CUNHA-NETO, Edecio; SILVA, Maria Elizabeth R.- The influence of population stratification on genetic markers associated with type 1 diabetes(2017) GOMES, Karla Fabiana Brasil; SANTOS, Aritania Sousa; SEMZEZEM, Cintia; CORREIA, Marcia Regina; BRITO, Luciano Abreu; RUIZ, Marcelo Ortega; FUKUI, Rosa Tsuneshiro; MATIOLI, Sergio Russo; PASSOS-BUENO, Maria Rita; SILVA, Maria Elizabeth Rossi daEthnic admixtures may interfere with the definition of type 1 diabetes (T1D) risk determinants. The role of HLA, PTPN22, INS-VNTR, and CTLA4 in T1D predisposition was analyzed in Brazilian T1D patients (n = 915), with 81.7% self-reporting as white and 789 controls (65.6% white). The results were corrected for population stratification by genotyping 93 ancestry informative markers (AIMs) (BeadXpress platform). Ancestry composition and structural association were characterized using Structure 2.3 and STRAT. Ethnic diversity resulted in T1D determinants that were partially discordant from those reported in Caucasians and Africans. The greatest contributor to T1D was the HLA-DR3/DR4 genotype (OR = 16.5) in 23.9% of the patients, followed by -DR3/DR3 (OR = 8.9) in 8.7%, -DR4/DR4 (OR = 4.7) in 6.0% and -DR3/DR9 (OR = 4.9) in 2.6%. Correction by ancestry also confirmed that the DRB1*09DQB1*0202 haplotype conferred susceptibility, whereas the DRB1*07-DQB1*0202 and DRB1*11DQB1*0602 haplotypes were protective, which is similar to reports in African-American patients. By contrast, the DRB1*07-DQB1*0201 haplotype was protective in our population and in Europeans, despite conferring susceptibility to Africans. The DRB1*10-DQB1*0501 haplotype was only protective in the Brazilian population. Predisposition to T1D conferred by PTPN22 and INS-VNTR and protection against T1D conferred by the DRB1*16 allele were confirmed. Correcting for population structure is important to clarify the particular genetic variants that confer susceptibility/protection for T1D in populations with ethnic admixtures.
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.conferenceObject Increased serum expression of miR-518d-3p and miR-618 in individuals with type 1 diabetes with microvascular chronic complications(2018) SANTOS-BEZERRA, D. P.; SANTOS, A. S.; GUIMARAES, G. C.; ADMONI, S. N.; PEREZ, R. V.; PELAES, T. S.; MACHADO, C. G.; PASSARELLI, M.; MACHADO, U. F.; QUEIROZ, M. S.; SILVA, M. E. R.; CORREA-GIANNELLA, M. L. C.- Skeletal muscle gene expression in older adults with type 2 diabetes mellitus undergoing calorie-restricted diet and recreational sports training - a randomized clinical trial(2022) SOARES, Diana Bento da Silva; SHINJO, Samuel Katsuyuki; SANTOS, Aritania Sousa; JESUS, Joyce de Cassia Rosa de; SCHENK, Simon; CASTRO, Gabriela Salim de; ZANOTELI, Edmar; KRUSTRUP, Peter; SILVA, Maria Elizabeth Rossi da; SOUSA, Maysa Vieira deAims: This study aimed to evaluate the impact of a 12-week calorie-restricted diet and recreational sports training on gene expressions IL-15, ATROGIN-1 and MURF-1 in skeletal muscle of T2D patients. Methods: Older adults with T2D (n = 39, 60 +/- 6.0 years, BMI 33.5 +/- 0.6 kg/m(2)) were randomly allocated to Diet+Soccer (DS), Diet+Running (DR) or Diet (D). The training sessions were moderate-to-high-intensity and performed 3 x 40 min/week for 12-weeks. Gene expression from vastus lateralis muscle obtained by qRT-PCR, dual-energy X-ray and fasting blood testing measurements were performed before and after 12-weeks. Statistical analysis adopted were two-way ANOVA and Paired t-test for gene expression, and RM-ANOVA test for the remainder variables. Results: Total body weight was reduced in similar to 4 kg representing body fat mass in all groups after 12-weeks (P < 0.05). HbA1c values decreased in all groups post-intervention. Lipids profile improved in the training groups (P < 0.05) after 12-weeks. ATROGIN-1 and MURF-1 mRNA reduced in the DS (1.084 +/- 0.14 vs. 0.754 +/- 1.14 and 1.175 +/- 0.34 vs. 0.693 +/- 0.12, respectively; P < 0.05), while IL-15 mRNA increased in the DR (1.056 +/- 0.12 vs. 1.308 +/- 0.13; P < 0.05) after 12-weeks intervention. Conclusion: Recreational training with a moderate calorie-restricted diet can downregulates the expression of atrophy-associated myokines and increases the expression of anti-inflammatory gene IL-15.
- PBMC of Recent-Onset Patients with Type 1 Diabetes Present a Differential Gene Expression Profile(2019) SANTOS, Aritania; CHEVILLARD, Christophe; GONFINETTI, Nelson; BERTONHA, Fernanda; MOREIRA-FILHO, Carlos; KALIL, Jorge; CUNHA-NETO, Edecio; SILVA, Maria Elizabeth
- The PTPN22 1858T allele but not variants in the proximal promoter region of IL-21 gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort(2013) MAINARDI-NOVO, D. T. O.; SANTOS, A. S.; FUKUI, R. T.; GAMBERINI, M.; CORREIA, M. R. S.; RUIZ, M. O.; MANGUEIRA, C. L. P.; MATIOLI, S. R.; VASCONCELOS, D. M.; SILVA, M. E. R.Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). We correlated the frequencies of islet and extra-pancreatic autoantibodies with genotypes from both loci. The case series comprised 612 T1AD patients and 792 HC. Genotyping of PTPN22 C1858T was performed on 434 T1AD patients and 689 HC. The 448 to +83 base pairs (bp) region of the IL-21 gene was sequenced in 309 Brazilian T1AD and 189 HC subjects. We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR)=1 center dot 94; P<0 center dot 001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. HLA-DR3/DR4 alleles predominated in T1AD patients. A heterozygous allelic IL-21 gene variant (g.-241 T>A) was found in only one patient. In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5-proximal region of the IL-21 gene were associated with T1AD risk. Patients with T1AD had increased frequencies of anti-islet-cell, anti-thyroid, anti-nuclear, anti-smooth muscle and anti-21-OH autoantibodies. The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies.
- Th17 pathway in recent-onset autoimmune diabetes(2018) FORES, Jessica Pereira; CRISOSTOMO, Lindiane Gomes; ORII, Noemia Mie; SANTOS, Aritania Sousa; FUKUI, Rosa Tsuneshiro; MATIOLI, Sergio R.; VASCONCELOS, Dewton de Moraes; SILVA, Maria Elizabeth Rossi daAims: Evaluate the participation of IL-17 pathway in T1D pathogenesis. T helper 17 cells are potent, highly inflammatory cells that produce interleukin 17A (IL-17A), considered a mediator of various immune disorders. However, their role in Type 1 diabetes (T1D) pathogenesis in humans is not totally elucidated. Methods: The expression of IL-17 Receptor A (IL-17RA) in peripheral T lymphocytes and IL-17A serum levels in recent-onset patients with T1D were compared with healthy controls. IL-17A gene variants were evaluated in a greater cohort. Results: Patients with recent-onset T1D (less than 6 months of diagnosis) exhibited lower expression of IL-17RA in CD3 + T (% of cells = 31.3% x 43.6%; p =.041) and CD4+ T cells (11.1% x 25.2%; p =.0019) and lower number of IL-17RA in CD4+ T cells (MFI = 1.16 x 4.56; p =.03) than controls. IL-17RA expression in CDS + T cells and IL-17A serum levels were similar in both groups. The coding regions and boundary intron sequences of IL17A were sequenced. Seventeen allelic variants, including three novel variants in exon 3 (3'UTR n) were identified, but no one was associated with T1D susceptibility, as well as the resulting haplotypes and diplotypes. The expression of IL-17RA was not correlated with metabolic variables (glucose and HbA1 c levels) or pancreatic autoantibodies titers. Conclusions: The lower expression of IL-17RA in CD3 + and CD4 + T cells suggests a reduced effect of IL-17A in immune response of recent-onset T1D patients, at least at peripheral tissues. IL-17A allelic variants were not related with T1D susceptibility.
- Progression of Type 1 Diabetes: Circulating MicroRNA Expression Profiles Changes from Preclinical to Overt Disease(2022) SANTOS, Aritania Sousa; FERREIRA, Ludmila Rodrigues Pinto; SILVA, Amanda Cabral da; ALVES, Lais Isidoro; DAMASCENO, Jullian Gabriel; KULIKOWSKI, Leslie; CUNHA-NETO, Edecio; SILVA, Maria Elizabeth Rossi daAims/Hypothesis. The role of microRNAs (miRNAs) in type 1 diabetes (T1D) pathogenesis and progression has been described but remains elusive. Objectives. To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D. Methods.We screened 377 serum miRNAs of 110 subjects divided into four groups: healthy individuals (control group) and patients at different stages of T1D progression, from the initial immunological manifestation presenting islet autoantibodies (AbP group) until partial and strong beta cell damage in the recent (recent T1D group) and long-term T1D, with 2 to 5 years of disease (T1D 2-5y group).Results. The results revealed 69 differentially expressed miRNAs (DEMs) in relation to controls. Several miRNAs were correlated with islet autoantibodies (IA2A, GADA, and Znt8A), age, and C-peptide levels, mainly from AbP, and recent T1D groups pointing these miRNAs as relevant to T1D pathogenesis and progression. Several miRNAs were related to metabolic derangements, inflammatory pathways, and several other autoimmune diseases. Pathway analysis of putative DEM targets revealed an enrichment in pathways related to metabolic syndrome, inflammatory response, apoptosis and insulin signaling pathways, metabolic derangements, and decreased immunomodulation. One of the miRNAs' gene targets was DYRK2 (dual-specificity tyrosine-phosphorylation-regulated kinase 2), which is an autoantigen targeted by an antibody in T1D. ROC curve analysis showed hsa-miR-16 and hsa-miR-200a-3p with AUCs greater than for glucose levels, with discriminating power for T1D prediction greater than glucose levels. Conclusions/Interpretation. Our data suggests a potential influence of DEMs on disease progression from the initial autoimmune lesion up to severe beta cell dysfunction and the role of miRNAs hsa-miR-16 and hsa-miR-200a-3p as biomarkers of T1D progression.
- Lack of association between IL27 gene variants and type 1 diabetes susceptibility(2013) SANTOS, Aritania S.; MELO, Maria E.; CRISOSTOMO, Lindiane C.; FUKUI, Rosa T.; MATIOLI, Sergio R.; SILVA, Maria Elizabeth R.Background: Recently, a new subpopulation of T cells, the Th17 subset, has been implicated in autoimmune diseases. Its development is influenced by IL-27, expressed in macrophages or dendritic cells. IL-27 blockage delays the onset of diabetes in non obese diabetes mouse, but its role in type 1 diabetes (T1D) in human has not been reported yet. The aim of this study was identify variants in the entire coding regions of IL-27 gene, including the 5' proximal region, and their possible association with the disease. Methods: Those regions were amplified by polymerase chain reaction followed by automatic sequencing and restriction fragments length polymorphisms. The cohort involved 614 individuals - 318 patients with T1D (19.6 +/- 11.2 y, 129 M/189F) and 296 healthy control subjects (30.3 +/- 13.2 y, 131 M/165F). Results: We identified eight allelic variants in the 5' proximal and coding regions of IL-27 gene, including two new variants: the c.-324 C > T in the 5' proximal region and the c.521 G > C in exon 5. None of these variants compromised transcription factor binding sites or the protein structure. The frequency of the alleles and genotypes of IL-27 variants did not differ between T1D patients and controls. There was no association between IL27 variants with gender, ethnicity, age at diagnosis of diabetes or presence of pancreatic and extrapancreatic autoantibodies. Conclusion: Our findings suggest that allelic variants in IL27 are not associated with susceptibility to T1D in a Brazilian population.