Abstracts Archive

The BB-rat monoclonal autoantibody IC2 and its beta-cell surface specificity discovered in the 1980th brought us the explore this unique autoantibody further by DNA cloning and sequencing (Genbank KP709022.1, KP709023.1) and to elucidate further its epitope specificity. The target seems to be certai...

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...

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  GAD antibodies (GADA) are used to identify patients with type 1 diabetes (T1D) and subjects at increased disease risk. They are, however, also detected in many healthy subjects without increased T1D risk. Radiobinding assays (RBAs) using N-terminally truncated GAD65 (96–585) inste...

Background: in type 1 diabetes (T1D), the chemokine CXCL10 recruits autoreactive T-lymphocytes in pancreatic islets, contributing to beta-cells destruction. CXCL10 is expressed by murine and human pancreatic islets in autoimmune diabetes, however the specific expression pattern has not been elucidat...

Background Oral administration of live genetically modified Lactococcus lactis (LL) secreting human proinsulin and IL-10 together with a short-course of low-dose anti-CD3 has been demonstrated to reverse T1D in NOD mice. Although LL therapy was successful in around 60% of NOD mice, 40% were metabo...

Immune monitoring by flow cytometry is a fast and highly informative way to assess changes in immunophenotypes longitudinally to study disease progression and the effects of immunotherapies. Utilising a total of less than 1 mL of peripheral blood, we developed a robust immune monitoring method to co...

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: The influence of ethnicity on the frequency of islet autoantibodies (AAb) in type 1 diabetes is unclear. We investigated differences in frequencies of AAbs to glutamate decarboxylase (GADA), islet autoantigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) in 3 ethnic groups with new-onset T1D:...

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: Insulin autoantibodies (IAA) are a key early marker of islet autoimmunity, particularly prevalent in young children who progress rapidly to Type 1 diabetes. Radiobinding assays (RBAs) are used to measure IAA but have limited specificity and sustainability. We evaluated the performance of...

Background: Mucosal associated invariant T (MAIT) cells are unconventional T cells, enriched in gut. They express an invariant T-cell receptor and recognize riboflavin metabolites from bacteria presented by MR1 molecules. Alterations in gut microbiota have been reported in patients with type 1 diab...

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: 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: 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: In certain autoimmune diseases, platelets and neutrophils are engaged in a vicious cycle of activation which promotes autoimmune disease. The aim of this study was to examine the contribution of platelet-neutrophil interactions to the development of Type 1 diabetes (T1D) in NOD mice. Met...

Background: Follicular T regulatory (Tfr) cells inhibit follicular T helper (Tfh) cells mediated by B cell responses. Tfh cells and B cells are involved in the pathogenesis of type 1 diabetes(T1D). However, the role of Tfr cells in T1D remains unclear. Methods: One hundred patients with T1D and 83 c...

Type 1 diabetes (T1D) exhibits substantial heterogeneity in disease course between subjects, with clinical variability in rate of progression before and after diagnosis. Autoantibodies are a reliable biomarker of disease progression but do not fully explain the mechanisms underlying clinical heterog...

Background: Type 1 diabetes (T1D) phenotype has been explored in predominantly white populations. People of non-white ethnicities diagnosed with T1D are reportedly less likely to be autoantibody positive. We studied differences in characteristics of people with T1D from 3 ethnicities:...

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...

Background Detection of beta-cell methylation specific cell-free DNA (cfDNA) offers a potential biomarker to monitor beta-cell death. Measuring multiple beta-cell specific targets should increase assay sensitivity and specificity. The aim of this study was to develop a robust, high throughput, multi...

We have shown that in type 1 diabetes (T1D) oxidative post-translational modification (oxPTM) generates neoepitopes and that antibodies to oxPTM insulin (oxPTM-INS-Ab) can potentially become robust biomarkers for T1D prediction and early diagnosis. Sensitivity, specificity, accuracy of oxPTM-INS-Ab ...

Aims: Knowledge of regions of autoantigens recognised by the immune system in Type 1 diabetes is crucial for the development of antigen-specific immune intervention to prevent Type 1 diabetes and for efficient disease prediction and diagnosis. We identified tetraspanin-7 (Tspan7), a multi-pass secre...

Background: The prevalence of diabetes associated antibodies (Ab) in Chinese patients recently diagnosed with adult-onset diabetes and the potential role of autoantibody markers for disease phenotype characterization were studied. Methods: 1383 recent-onset adult diabetic patients (mean age 54 years...

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 beta-cell itself has become recognized as a central player in the pathogenesis of type 1 diabetes (T1D), with the generation of neo-antigens in response to inflammation as potential trigger for breaking immune tolerance. Given the heterogeneity of T1D, the identification of ne...

Aims:Autoantibodies to islet autoantigens are important for identification of individuals at risk of Type 1 diabetes and their selection for immune intervention. Tetraspanin-7 (Tspan7) has been identified as an autoantigen in Type 1 diabetes, equivalent to the autoantibody target previously describe...

BACKGROUND: Tetraspanin 7 is an integral membrane protein that is expressed in the pancreatic beta cells. It is also an autoantigen target in type 1 diabetes. Autoantibodies to tetraspanin7 are found in 35% of patients at disease onset as compared to < 1% of healthy control subjects. Since tetraspan...

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: 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. ...