Abstracts Archive

Background Coxsackievirus B (CVB) viruses are associated with Type 1 diabetes (T1D), however, whether they are causal remains unknown. A strategy to determine their involvement in T1D could involve vaccination of at-risk individuals with a vaccine targeting the six known CVB serotypes (CVB1-6) and s...

Background Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human t...

BackgroundThe course of beta cell function decline is very heterogenous after T1D onset. We aimed to describe the natural course of residual insulin secretion over the first year after T1D diagnosis and to determine the predictors of the partial remission within metabolic and immune parameters. Meth...

Background: Regulatory T cells (Tregs) play an important role in maintaining tolerance to self-antigens. Defects in frequency and function of polyclonal Tregs have been reported in type 1 diabetes (T1D). However, the characteristics of islet-specific Tregs have not yet been determined in juvenile-on...

Background Recently, we reported a novel β cell population with compromised β cell signatures that are able to survive and proliferate as a result of autoimmunity during the disease progression in NOD mice. The intrinsic vulnerability of β cells to ER stress and oxidative stress-induced dysf...

Background Inflammatory cytokines, particularly the interferons, have been implicated in the pathogenesis of type 1 diabetes (T1D). Interferon-stimulated genes, including those that encode MHC proteins, are pathological hallmarks of the pancreatic islet during the development of T1D in both humans a...

Background: The reeducation of the immune system is crucial to tackle autoimmunity in type 1 diabetes (T1D). Since self–tolerance is induced by apoptotic cell clearance (a process known as efferocytosis), a nanotherapy consisting of liposomes rich in phosphatidylserine (PS) encapsulating beta–ce...

  We recently established that hybrid insulin peptides (HIPs), formed spontaneously in islet beta-cells by fusion of insulin C-peptide fragments to peptides of Chromogranin A (ChgA) or Islet Amyloid Polypeptide (IAPP), are ligands for diabetogenic CD4 T cell clones. The goal of this study was t...

  Background. Type 1 diabetes (T1D) is an autoimmune disease in which the immune system destroys insulin-producing pancreatic beta-cells. Although pro-insulin is probably the primary autoantigen, other non-beta-cell specific proteins behave as autoantigens. Data indicate that such proteins can ...

Type 1 diabetes (T1D) is primarily characterized by immune-mediated destruction of pancreatic beta-(β)-cells resulting in loss of insulin production. Its incidence is significantly increasing in developed countries and there is currently no prevention or cure. Existing rodent and in vitro models la...

Multiple studies suggest that the strength of the T cell receptor (TCR) signal leading to regulatory T cell (Treg) development and function is unique and distinct from effector T cells (Teffs). However, functional implications of a unique Treg TCR repertoire in autoimmune diabetes are largely unknow...

Background: Inflammation and oxidative stress in the pancreas amplifies various post-translational modifications (PTMs) on self-proteins. The loss of immune tolerance to PTMs within the stressed islets subsequently impacts the autoreactive T cell epitope repertoire and contributes to the destructi...

Background: Type 1 diabetes (T1D) is almost invariably preceded by positivity for islet autoantibodies. Recent studies have shown that circulating T follicular helper (Tfh) cells are increased in patients with T1D. Together, these findings support an important role for T-B-cell interactions in T1D p...

Background The CRISPR-Cas9 system has been developed into a phenotype screening strategy. Using lentiviral delivery of a large collection of gRNAs, thousands of genes can be targeted for Cas9-mediated disruption in mammalian cells. Growing evidence supports ER stress as a target to prevent the initi...

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: 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 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...

Background: Insulin is a target of autoimmunity that destroys beta cells in type 1 diabetes (T1D). In the NOD mouse model of T1D, insulin delivered to the nasal mucosa induced regulatory T cells and decreased diabetes incidence. We reported two human trials demonstrating intranasal insulin was safe ...

Insufficient regulatory T cell (Treg) control of autoreactive T cell-mediated destruction of beta-cells contributes to type 1 diabetes (T1D). Multiple therapeutic strategies to restore a normal immunoregulatory balance and stop T1D progression are in development and testing. However, a major challen...

Background: Defining clinical endpoints is challenging in type1 diabetes (T1D) trials. While stimulated C-peptide following mixed meal tolerance test (MMTT) is the gold standard, it is cost- and time- intensive to measure. Furthermore, it fails to capture the clinical benefit expected with beta cell...

Background: In the pre-clinical phase of disease, monitoring anti-islet antibodies is the only means to evaluate b cell destruction. As T1D is a T cell mediated disease, and can develop in agammaglobulinemia patients, detecting and profiling activated anti-islet CD4 T cells from peripheral blood wou...

Background:Preclinical studies suggest that blockade of pro-inflammatory IL-17/IFN-γ secreting T cells inhibits the T1D autoinflammatory response. We assessed the safety and optimal dosing of ustekinumab (a monoclonal antibody targeting the IL-17/IFN-γ pathway) for the treatment of adult recent-on...

The role of type 17 immune responses in the pathogenesis of type 1 diabetes (T1D) has been tested in multiple studies however the importance of these pathways remains enigmatic. The function of the prototypic IL-17 family cytokine, IL-17A, has been tested most extensively and while blockade of IL-17...

Background. Tolerogenic vaccinations using beta-cell antigens (Ags) targeted by autoimmune T-cells are attractive for T1D prevention due to their selectivity and safety, but have not hold their promise in clinical trials. This is probably due to the late time of intervention, once the autoimmune rea...

Neonatal period is a critical window when central tolerance is established in an Autoimmune Regulator (Aire). However, not all self-antigens are expressed downstream of Aire and tolerance to some tissue restricted antigens might rely in part on peripheral dendritic cells (DCs). The relative contrib...