Project description:Genome-wide expression kinetics of children with Type 1 diabetes (T1D) -associated autoantibodies or progression towards clinical T1D, compared to healthy matched controls .
Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis. 357 peripheral blood RNA samples from 10 autoantibody-positive children (Case) and their matched controls (Control) or alternatively 18 prediabetic children (T1DCase) and their matched controls (T1DControl) were analyzed with Affymetrix U219 gene array, in order to study the gene expression changes occuring during the pathogenesis of Type 1 diabetes (T1D). Each case child (positive for T1D-specific autoantibodies) was matched with a persistently autoantibody-negative control child, with the same HLA-DQB1 risk category, gender, and place and date of birth. Seroconversion is determined as the first detection of T1D-specific autoantibody/autoantibodies (ICA titre >4 JDFU, IAA >3.47 RU, GADA >5.4 RU, IA-2A >0.43 RU, ZnT8A >0.61 RU). Two control children were selected for T1D cases 3, 5, 13 and 17. Case5 & T1DCase15 and Case7 & T1DCase3 share the same matched control. Sample T1DControl7_4 was excluded from the final analysis as an outlier, resulting in 356 total Samples listed below.
Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis. 63 peripheral blood RNA samples from 6 autoantibody-positive children (Case) and their matched controls (Control) were analyzed with Illumina Sentrix WG-6 v2 genome-wide arrays, in order to study the gene expression changes occuring during the pathogenesis of Type 1 diabetes (T1D). Each case child (positive for T1D-specific autoantibodies) was matched with a persistently autoantibody-negative control child, with the same HLA-DQB1 risk category, gender, and place and date of birth. Seroconversion is determined as the first detection of T1D-specific autoantibody/autoantibodies (ICA titre >4 JDFU, IAA >3.47 RU, GADA >5.4 RU, IA-2A >0.43 RU, ZnT8A >0.61 RU).
Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis. 58 peripheral blood RNA samples from 4 autoantibody-positive children and their matched controls were analyzed with Illumina Sentrix WG-6 v2 genome-wide arrays, in order to study the gene expression changes occuring during the pathogenesis of Type 1 diabetes (T1D). Each case child (positive for T1D-specific autoantibodies) was matched with a persistently autoantibody-negative control child, with the same HLA-DQB1 risk category, gender, and place and date of birth. Seroconversion is determined as the first detection of T1D-specific autoantibody/autoantibodies (ICA titre >4 JDFU, IAA >3.47 RU, GADA >5.4 RU, IA-2A >0.43 RU, ZnT8A >0.61 RU).
Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis. 247 peripheral blood RNA samples from 18 prediabetic children and their matched controls were analyzed with Illumina Human HT-12 Expression BeadChips version 3 arrays, in order to study the gene expression changes occuring during the pathogenesis of Type 1 diabetes (T1D). Each case child (with T1D-specific autoantibodies) was matched with a persistently autoantibody-negative control child, with the same HLA-DQB1 risk category, gender, and place and date of birth. Two control children were selected for T1D cases 3, 5, 13 and 17. Seroconversion is determined as the first detection of T1D-specific autoantibody/autoantibodies (ICA titre >4 JDFU, IAA >3.47 RU, GADA >5.4 RU, IA-2A >0.43 RU, ZnT8A >0.61 RU).
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:Type 1 diabetes (T1D) usually has a preclinical phase identified by the presence of circulating autoantibodies to pancreatic islet antigens, and most young children who have multiple autoantibodies progress to diabetes within 10 years. While autoantibodies denote underlying islet autoimmunity, how this process is initiated and then progresses to clinical diabetes on a background of genetic susceptibility is not clearly understood. We analysed gene expression by RNA-seq in four types of immune cells from five genetically at-risk children with islet autoantibodies who progressed to diabetes in ≤ 3 years (‘progressors’) and in five at-risk children matched for sex, age and HLA who had not progressed to diabetes (‘non-progressors’).
Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis.
Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis.