Expression data from peripheral blood mononuclear cell in patients with type 1 diabetes compared with normal controls
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ABSTRACT: Type 1 diabetes mellitus (T1D) is a common autoimmune disease mediated by autoimmune attack against pancreatic b cells.Dys-regualtion of the component of peripheral blood mononuclear cells (PBMCs), including T-cells and B-cells, and smaller amounts of NK cells and dendritic cells, have all been implicated in this process This study sought to identify T1D associated differently expressed genes in the peripheral blood mononuclear cell (PBMC). Peripheral blood mononuclear of newly diagnosed type1 diabetes patients and normal controls were purified by LymphoprepTm gradient purification according to the manufacturer’s instructions (Axis-Shield PoC AS, Oslo, Norway) for futher microarray analysis.
Project description:Type 1 diabetes mellitus (T1D) is a common autoimmune disease mediated by autoimmune attack against pancreatic b cells. It has been reported that dys-regulation of microRNAs (miRNAs) may contribute to the pathogenesis of autoimmune diseases, including T1D. This study sought to identify T1D associated miRNAs in the peripheral blood mononuclear cell (PBMC). Peripheral blood mononuclear of newly diagnosed type1 diabetes patients and normal controls were purified by LymphoprepTm gradient purification according to the manufacturerM-bM-^@M-^Ys instructions (Axis-Shield PoC AS, Oslo, Norway) for futher microarray analysis.
Project description:Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) was the first therapeutic approaches that can improve beta cell function in type 1 diabetic (T1D) patients. This study was designed to investigate the potential mechanisms involved.We applied AHST to nine T1D patients diagnosed within six months and analyzed the acute response in peripheral blood genomic expression profiling at the six-month follow-up. Peripheral blood mononuclear of newly diagnosed type1 diabetes patients at diagnosis and at six months post-transplantation by autologous peripheral stem cell were purified by LymphoprepTm gradient purification according to the manufacturer's instructions (Axis-Shield PoC AS, Oslo, Norway) for futher microarray analysis.
Project description:Type 1 diabetes mellitus (T1D) is a common autoimmune disease mediated by autoimmune attack against pancreatic b cells.Dys-regualtion of the component of peripheral blood mononuclear cells (PBMCs), including T-cells and B-cells, and smaller amounts of NK cells and dendritic cells, have all been implicated in this process This study sought to identify T1D associated differently expressed genes in the peripheral blood mononuclear cell (PBMC).
Project description:Type 1 diabetes mellitus (T1D) is a common autoimmune disease mediated by autoimmune attack against pancreatic b cells. It has been reported that dys-regulation of microRNAs (miRNAs) may contribute to the pathogenesis of autoimmune diseases, including T1D. This study sought to identify T1D associated miRNAs in the peripheral blood mononuclear cell (PBMC).
Project description:Type 1 Diabetes (T1D) is considered to be a Th1 autoimmune disease characterised by an absolute lack of insulin caused by an autoimmune destruction of the insulin producing pancreatic beta cells. Th1 lymphocytes are responsible for the infiltration of the islets of Langerhans and for the cytokine release that supports cytotoxic (Tc) lymphocytes to mediate destruction of the beta cells. The preclinical disease stage is characterized by the generation of the self-reactive lymphocytes that infiltrate the pancreas and selectively destroy the insulin-producing beta cells present in the islets. Other cellular immune mechanisms regarding immunoregulation and antigen presentation and processing are involved in T1D pathogenesis as well. Our aim was to identify genes involved in the corresponding signalling cascades, especially those which may serve as promising diagnostic tools for the identification of persons in the prediabetic phase of the disease. We addressed the question by analysing gene expression profiles of freshly isolated peripheral blood mononuclear cells in type 1 diabetes patients, their first degree relatives divided according to their autoantibody status, and healthy controls. 9 T1D-patients versus 10 first degree relatives versus 10 healthy controls
Project description:Type 1 diabetes (T1D) is an autoimmune disease caused by selective destruction of insulin producing pancreatic beta-cells in the islets of the Langerhans. The progression to clinical diabetes is characterized by the appearance of autoantibodies against islet cells (ICA) and beta-cell-specific antigens (IAA, IA-2 and GADA), which are considered the first markers signifying onset of autoimmunity. The mechanisms initiating or enhancing the autoimmune process remain poorly understood. Transcriptomic profiling on whole blood samples provides an approach for monitoring T1D disease process. In these investigations of pathways that are changed during the disease process, we have analyzed RNA from longitudinal peripheral blood samples of children who have developed T1D associated autoantibodies and eventually clinical type 1 diabetes . All study subjects were participants of the Type 1 Diabetes Prediction and Prevention (DIPP) study in Finland (38). Whole-blood RNA samples were collected during periodic clinic visits, typically at 3 to 12 month intervals. 2.5 ml venous blood was drawn into PAXgene Blood RNA tubes (Becton-Dickinson) and stored at -70°C. T1D-associated autoantibodies were measured from blood samples taken at each visit. Prospective samples from 3 children who developed T1D (subjects T1D_1 - T1D_3) and 2 children who developed ICA (subjects ICA_1 and ICA_2) during the DIPP follow-up were selected to the present study. Control children for the T1D cases (subjects T1D_C1 - T1D_C2) were matched for age, gender, birth place and HLA-genotype, from families who have no first-degree relatives with T1D. All samples (n=60) were processed and hybridized on Affymetrix Human Genome U133 Plus 2.0 arrays.
Project description:To identify genes with expression levels that are associated with T1D progression from AbP (islet autoantibody positive), global gene expression changes were analyzed in AbP subjects with different T1D progression rate. Total RNA were obtained from peripheral blood mononuclear cells (PBMC) of total 36 AbP subjects with different T1D progression rate. Microarray was carried out to analyze gene expression and Kaplan-Meier survival analysis and log-rank test were used to compare differences in diabetes-free survival between groups classified based on single gene expression.
Project description:Objective: We hypothesized that type 1 diabetes (T1D) is accompanied by changes in gene expression in peripheral blood mononuclear cells (PBMCs) due to dysregulation of adaptive and innate immunity, counterregulatory responses to immune dysregulation, insulin deficiency and hyperglycemia. Research Design and Methods: Microarray analysis was performed on PBMCs from 43 patients with newly diagnosed T1D, 12 patients with newly diagnosed type 2 diabetes (T2D) and 24 healthy controls. One and four month follow-up samples were obtained from 20 of the T1D patients. Results: Microarray analysis identified 282 genes differing in expression between newlydiagnosed T1D patients and controls at a false discovery rate of 0.05. Changes in expression of interleukin-1β (IL1B), early growth response gene 3 (EGR3), and prostaglandin-endoperoxide synthase 2 (PTGS2) resolved within four months of insulin therapy and were also observed in T2D suggesting that they resulted from hyperglycemia. With use of a knowledge base, 81/282 genes could be placed within a network of interrelated genes with predicted functions including apoptosis and cell proliferation. IL1B and the MYC oncogene were the most highly-connected genes in the network. IL1B was highly overexpressed in both T1D and T2D, whereas MYC was dysregulated only in T1D. Conclusion: T1D and T2D likely share a final common pathway for beta cell dysfunction that includes secretion of interleukin-1β and prostaglandins by immune effector cells, exacerbating existing beta cell dysfunction, and causing further hyperglycemia. The results identify several targets for disease-modifying therapy of diabetes and potential biomarkers for monitoring treatment efficacy. Keywords: Diabetes, microarray analysis, peripheral blood mononuclear cells
Project description:Type 1 Diabetes (T1D) is considered to be a Th1 autoimmune disease characterised by an absolute lack of insulin caused by an autoimmune destruction of the insulin producing pancreatic beta cells. Th1 lymphocytes are responsible for the infiltration of the islets of Langerhans and for the cytokine release that supports cytotoxic (Tc) lymphocytes to mediate destruction of the beta cells. The preclinical disease stage is characterized by the generation of the self-reactive lymphocytes that infiltrate the pancreas and selectively destroy the insulin-producing beta cells present in the islets. Other cellular immune mechanisms regarding immunoregulation and antigen presentation and processing are involved in T1D pathogenesis as well. Our aim was to identify genes involved in the corresponding signalling cascades, especially those which may serve as promising diagnostic tools for the identification of persons in the prediabetic phase of the disease. We addressed the question by analysing gene expression profiles of freshly isolated peripheral blood mononuclear cells in type 1 diabetes patients, their first degree relatives divided according to their autoantibody status, and healthy controls.
Project description:The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D, HC, and healthy T1D sibling cohorts. In addition, we examined T1D progression by looking at longitudinal samples.