Abstracts Archive

The Autoimmunity Screening for Kids (ASK) program is design to determine the prevalence of pre-symptomatic type 1 diabetes (T1D) and celiac disease (CD) in Denver general population children 1-17 y old. In the initial 16 months, 8120 children were screened for GADA, IA-2A, mIAA as well as for transg...

Background : Intestinal epithelial integrity reflects a healthy gut microbiome and both may be compromised in type 1 diabetes (T1D). We aimed to characterise the gut microbiome, bacterial products and small intestinal permeability longitudinally in children with islet autoimmunity (IA) . Methods :&...

 Auto-reactive CD8 T-cells play an important role in the destruction of pancreatic β-cells resulting in type 1 diabetes (T1D). However, the phenotype of these auto-reactive cytolytic CD8 T-cells has not yet been extensively described. We used high-dimensional mass cytometry to phenotype auto- (pre...

  Hmgb1 is an evolutionarily conserved chromosomal protein. It was recently re-discovered to be a potent innate alarmin implicated in both innate and adaptive immune response when it is present extracellularly. Hmgb1 can be either passively released by damaged cells or actively secreted by activate...

Hyaluronan (HA), an extracellular matrix polysaccharide, is implicated in the pathogenesis of both type 1 diabetes mellitus (T1DM) as well as type 2 diabetes mellitus (T2DM) and has been suggested to be increased in these diseases due to hyperglycemia. Here, we examined the serum and tissue distrib...

Background: Primary prevention of type 1 diabetes (T1D) requires early intervention in genetically at-risk infants. Neonates and infants who are at increased risk to develop type 1 diabetes can be identified using genetic markers. The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD)...

Background: Induction of Tregs in the gut can promote tolerance towards pancreas associated antigens in type 1 diabetes. In this study, we induced colonic Tregs (cTregs) by administering sodium butyrate in NOD mice and analyzed their migratory potential towards pancreas and pancreatic lymph nodes (P...

Background: Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin producing β-cells. Immunotherapeutic prevention before disease onset has the best potential to preserve β-cell function, and thus, it is crucial to understand the autoimmune process leading to T1D. Although imm...

Introduction The role of diet in type 1 diabetes (T1DM) development is poorly understood, perhaps due to differences in biological processing of nutrition. Metabolites, which mark response to diet, in combination with reported intake may help elucidate this role. Therefore, we examined the associati...

BACKGROUND: Antigen-specific immunotherapies (ASIT) may rely on targeting as many disease-relevant T cells as possible for efficacy. This clearly requires an appropriate delivery system that protects antigens or antigen-encoding vectors from degradation and facilitates their drainage to lymphoid tis...

Background Insulin and chromogranin A (ChgA) are autoantigens for CD4 T cells in the NOD mouse model of type-1 diabetes. Natural peptides from Insulin (B:9-23) and chromogranin A (WE14) are both weak antigens for diabetogenic CD4 T cells. Studies from our lab show that these peptides can be converte...

Objectives: The gut virome is an important component of the microbiome. It comprises human viruses including known candidates for triggering islet autoimmunity, as well as phages that interact with the gut bacteriome. The association between the gut virome and initiation of islet autoimmunity is elu...

Background: The first appearing diabetes-associated autoantibody (Ab) has been shown to vary risk of T1D. Here, we assessed risk of autoantigen spreading by appearance of the second-appearing Ab and further progression to T1D in the Environmental Determinants of Diabetes in the Young (TEDDY) study. ...

Human CD4 T cells recognize the c-terminally modified insulin B:9-23 peptide in the same fashion as mouse diabetogenic T cells Yang Wang1,2, Tomasz Sosinowski3, Andrey Novikov1, Frances Crawford4, Howard W. Davidson2,3, Laurent Gapin2, John Kappler2,4, and Shaodong Dai1,2 1Department of Pharmaceutic...

Objective: T-cell-mediated destruction of pancreatic β cells leads to Type 1 diabetes Mellitus (TIDM). Tetraspanin-7(TSPAN7) has recently been identified as an autoantigen in T1DM patients. Autoreactive CD8+T cell recognize β-cell-derived epitopes in the context of major histocompatibility complex...

Background: Type 1 diabetes (T1D) is the result of the progressive attack against insulin-producing β-cells by the immune system. Despite many attempts, effective interventions to preserve residual β-cells functions are lacking. Immunomodulation with autoantigens could potentially constitute the m...

Introduction: Most young children with multiple islet autoantibodies (mAabs) develop diabetes by 10 years of follow-up. Using data from several longitudinal studies of diabetes, we identified a group of slow progressors; children and adults who remain diabetes free for at least 10 years following mA...

Background: Maternal microchimerism (MMc), the transmission of small quantities of maternal cells to the fetus, is relatively common and persists into adult life. MMc is thought to be involved in tissue regeneration and/or immunenological tolerance. MMc has been postilated to play a role in autoimmu...

Background: MicroRNAs are a class of small non-coding RNAs that regulate gene expression, which are involved in β-cell function and differentiation; their alteration may contribute to the development of type 1 diabetes(T1D). The aim of this study was to analyze their expression profile in pancreati...

People suffered from type 2 diabetes were change in eating habits in diet. Fructose consumption increase incidence of hepatic manifestation of metabolic syndrome including insulin resistance and diabetes mellitus. In recent years, small molecular oligopeptides were used in prevention and...

Background: The presence of islet-associated autoantibodies is predictive of type 1 diabetes (T1D) onset, with limited reports indicating its specific association with pancreatic insulitis in the absence of beta cell loss. Recent efforts suggest a composite T1D genetic risk score (GRS) enhances pred...

Background In a previous study conducted on subjects newly diagnosed with Type 1 diabetes (T1D) we measured multiple parameters (IFN-γ, IL-10 production by autoreactive CD4 T cells against a range of target autoantigens as well as autoantibodies (AAb)) and used a multi-dimensional, unbiased analyti...

Loss of pancreatic islet beta cells precedes the clinical onset of autoimmune (type 1) diabetes. The prodrome can go on for months to years during which time autoantibodies against insulin (IAA), GAD65 (GADA), islet antigen-2 (IA-2A) or ZnT8 (ZnT8A) may be present alone or in various combinations. T...

Background: The remission of T1D is a clinically valuable period whose extension would greatly benefit the patients. We investigated whether the ability of newly diagnosed T1D patients to conserve beta-cell capacity is transmissible through the gut microbiome to germ-free (GF) non-obese diabetic (NO...

  Insulin-dependent diabetes mellitus (Type 1 diabetes, T1D) is an autoimmune disease where autoreactive T lymphocytes destroy pancreatic beta cells. Common human autoimmune diseases show quantitative or qualitative T regulatory (Treg) defects. We previously reported a defect in CD4+ Tregs cell pro...

The long-term success of islet transplantation as a diabetes treatment depends on halting underlying recurrence of autoimmunity driven by pre-primed autoreactive effector T cells. Low-dose anti-CD3 monoclonal antibodies combined with live Lactococcus lactis secreting proinsulin and IL-10 (LL-PINS+IL...

Background: Insulin is an essential autoantigen in human and murine type 1 diabetes. Thymic negative selection is critical for the removal of self-reactive cells, while peripheral regulation maintains tolerance to self-antigen. As low-affinity autoreactive cells escape central tolerance, peripheral ...

Background: Vitamin D circulates mainly as 25-hydroxyvitamin D (25OHD) bound to vitamin D-binding protein (DBP), and may influence immunity. DBP concentration doubles during pregnancy, and higher maternal DBP concentration during late pregnancy was associated with lower risk of childhood type 1 diab...

Background: Gestational diabetes (GDM) is defined as glucose intolerance that presents during pregnancy. It increases the risk of developing diabetes later in life. Recent studies have revealed an important role of microRNAs (miRNAs) in the pathogenesis of diabetes, including GDM. However, there is ...

Background Adults with type 1 diabetes (T1D) have smaller pancreata and there is growing evidence for accompanying immune infiltrates in the exocrine pancreas and subclinical exocrine dysfunction. Beta cells comprise 200 ug/g. Conclusion Pancreatic area in transverse and longitudinal planes is redu...