ARITANIA SOUSA SANTOS
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
LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- 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.
- 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.
- CD226 rs763361 Is Associated with the Susceptibility to Type 1 Diabetes and Greater Frequency of GAD65 Autoantibody in a Brazilian Cohort(2014) MATTANA, Teresa Cristina Colvara; SANTOS, Aritania Sousa; FUKUI, Rosa Tsuneshiro; MAINARDI-NOVO, Debora Teixeira Oliveira; COSTA, Vinicius Silva; SANTOS, Rosa Ferreira; MATIOLI, Sergio Russo; SILVA, Maria Elizabeth Rossi daCD226 rs763361 variant increases susceptibility to type 1 diabetes (T1D) in Caucasians. There is no data about CD226 variants in the very heterogeneous Brazilian population bearing a wide degree of admixture. We investigated its association with T1D susceptibility, clinical phenotypes, and autoimmune manifestations (islet and extrapancreatic autoantibodies). Casuistry. 532 T1D patients and 594 controls in a case-control study. Initially, CD226 coding regions and boundaries were sequenced in a subset of 106 T1D patients and 102 controls. In a second step, two CD226 variants, rs763361 (exon 7) and rs727088 (3' UTR region), involved with CD226 regulation, were genotyped in the entire cohort. C-peptide and autoantibody levels were determined. No new polymorphic variant was found. The variants rs763361 and rs727088 were in strong linkage disequilibrium. The TT genotype of rs763361 was associated with TID risk (OR = 1.503; 95% CI = 1.135-1.991; P = 0.0044), mainly in females ( P = 0.0012), greater frequency of anti-GAD autoantibody (31.9% x 24.5%; OR = 1.57; CI = 1.136-2.194; P = 0.0081), and lower C-peptide levels when compared to those with TC + CC genotypes (0.41 +/- 0.30 ng/dL versus 0.70 +/- 0.53 ng/dL P = 0.0218). Conclusions. The rs763361 variant of CD226 gene (TT genotype) was associated with susceptibility to T1D and with the degree of aggressiveness of the disease in T1D patients from Brazil. Ancestry had no effect.
- Protective effect of interleukin-23A (IL23A) haplotype variants on type 1A diabetes mellitus in a Brazilian population(2013) COSTA, V. S.; SANTOS, A. S.; FUKUI, R. T.; MATTANA, T. C. C.; MATIOLI, S. R.; SILVA, M. E. R.The Interleukin 23 (IL-23) has a central role in autoimmunity. Allelic variants of p19 subunit of IL-23 (IL23A) and IL-23 receptor. (IL23R) genes and increased IL-23 serum concentrations were associated with autoimmune diseases. We therefore searched for variants of IL23A and IL23R that could predispose to Type 1 diabetes (T1D). The coding regions and boundary intron sequences of IL23A were sequenced. Variants of IL23A and of IL23R were also genotyped. Pancreatic and extrapancreatic autoantibodies and IL-23 serum levels were determined. The cohort involved 370 patients with T1D and 351 healthy control subjects. We observed only one coding IL23A variant (rs11171806 G > A) out of the 6 described in databases. As the G alleles of rs11171806 and rs2066808 variants of IL23A gene were in strong linkage disequilibrium (D' = 0.825 for controls, p < 2.0 x 10(-6) and D' = 0.902, p < 2.0 x 10(-17) for patients), further analyses were performed with the haplotypes. The GG haplotype was more frequent in controls (16.7%) than in T1D patients (9.5%), conferring a protection to T1D (OR = 0.53; pc = 0.0003). No association was found between IL23A allelic variants with age at diagnosis of diabetes, C-peptide levels or frequency of autoantibodies. IL23R variants (rs10889677 and rs11209026) frequency and IL-23 serum concentrations were similar between groups. The GG haplotype of IL23A variants (rs11171806 and rs2066808) was protective against T1D. IL23R variants (rs11209026 and rs10889677) were not associated with T1D. IL-23 serum concentrations did not differ between groups.