Abstracts Archive

  Antigen-specific therapy aims to modify inflammatory T cell responses in type 1 diabetes (T1D) and restore immune tolerance. One strategy employs GAD-Alum to induce a TH2 response to regulate pathological TH1 autoimmunity. We explored the cellular/molecular mechanism of GAD-Alum action in the set...

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...

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...

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 Vitamin C might protect beta cells from oxidative damage and thus prevent islet autoimmunity (IA) and type 1 diabetes mellitus (T1DM). We studied the association of plasma vitamin C concentration with the risk of developing T1DM related outcomes and examined whether missense single nucle...

Steady glycaemic control is crucial for T1D patients, however it remains difficult to achieve with exogenous insulin therapy. An interesting and unexplored therapeutic option is the use of genetically modified adeno-associated virus (AAV) vectors that have proved successful in the cure of monogenic ...

Depending on population, 0.1-1.0% of children will develop autoimmunity to pancreatic beta cells in childhood and subsequently type 1 diabetes (T1D). The risk is increased more than 10x if a child has a family history of T1D. We explored the interaction between genetic susceptibility and this excess...

    Background: The gut microbiome shapes the development of a healthy immune system and may be altered in children in the pre-clinical stage of type 1 diabetes (T1D). The Environmental Determinants of Islet Autoimmunity (ENDIA; endia.org.au) study investigates environment-gene interactions in t...

Objectives: Microbiome studies in type 1 diabetes (T1D) to date are limited to populations of Europe (mostly North-Eastern), with one study each from Mexico, the USA, and China. We therefore sought to characterize the gut bacteriome and virome in children after onset of T1D along with age- and place...

High resolution mapping of genetic risk by GWAS, eQTL and imputation has identified 52 regions of genetic risk for type 1 diabetes, and these loci are highly enriched for immune function. When combined with functional annotation data it is also clear that the genetic risk of T1D is highly enriched i...

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 :&...

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...

The majority of disease associated variants in type 1 diabetes (T1D) are located in non-coding DNA and are enriched in areas of open or active chromatin. Functional annotation of the genome has revolutionised our ability to understand the “grammar” of the non-coding genome and integration of suc...

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. Environmental factors are crucial in the pathogenesis of type 1 diabetes (T1D). In this sense, betamethasone –a synthetic glucocorticoid administered to women at risk of preterm delivery to improve newborn survival– could alter the development of foetal immune system, influencing the...

  Fecal microbiota transplantation (FMT) is a potential therapy for metabolic syndrome and diabetes. It has been shown that FMT increased insulin sensitivity in metabolic syndrome. Here we show that FMT significantly restored glucose homeostasis in refractory diabetes even if the islet function wer...

Background: Genome-wide association studies have demonstrated that variations in intron 19 of CLEC16A, in the 16p13.13 region of the human genome, are associated with risk of type 1 diabetes (T1D). This region is also associated with IgA deficiency and microbial diversity in the human gut. No conse...

Background Homeostatic interactions between immune cells and microbes are essential for inducing tolerance, while disruptions to these interactions can modify disease susceptibility. Recent studies, including our own, suggest that commensals are important environmental components of type 1 diabetes ...

Tissue-specific autoimmune diseases are assumed to arise from the malfunction of two checkpoints for immune tolerance: defect in the elimination of autoreactive T-cells in the thymus, and activation of these T-cells by the corresponding autoantigens in periphery. However, evidence for this model an...

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 risk of Type 1 Diabetes (T1D) comprises genetic and environmental components, which both could be mediated by DNA methylation (DNAm). Previous studies established associations between DNAm and T1D GWAS variants, but it is unclear whether these associations indicate causation or were ...

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: We have identified a common defect in the Tregs of patients with certain autoimmune and allergic diseases: diminished inhibition of desensitization of their Treg IL-2 receptors (IL-2R) in response to low dose IL-2. Desensitization, or “turning off the IL-2R” occurs whe...

Background;This is a study of 282 research subjects in vivo (n=52) and in vitro (n=230) related to the clinical and metabolic effects of repeat BCG vaccines in type 1 diabetic subjects (T1D). Methods:We report on a randomized, placebo-controlled examination of adult subjects with long-term type 1 di...

Background and AimsStudies of pancreatic tissue gathered soon after onset of Type 1 diabetes have revealed the existence of two, age-related, immune phenotypes in inflamed islets (CD20Hi & CD20Lo). Since these also vary according to the proportion of residual insulin containing islets retained at di...

Background Multiple genetic factors associated with an elevated risk of type 1 diabetes (T1D) are thought to affect the development and maturation of immune cell subsets. T1D-associated polymorphisms may affect the function of the immune system by altering the frequency or phenotype of immune cell s...

The exact cause for T1D is unknown, but the contribution of genetic and environmental factors, leading to a breakdown in immune tolerance has been proposed. Genetic data strongly link the breakdown in tolerance to alterations in the transcriptional program in CD4+ T cells. Various environmental fa...

Background: The purpose of this study was to obtain comprehensive gene expression datasets from a large number of individual islets, with defined pathological phenotypes, from organ donors with different clinical stages of type 1 diabetes. Here we will present results from an analysis that compared ...