Abstracts Archive

  Immune-based therapies for T1D need to focus on restoring self-tolerance without the need for chronic immunosuppression. CD4+Foxp3+ regulatory T-cells (Tregs) maintain immunological tolerance and can be harnessed to control autoimmunity and prevent transplant rejection. However, clinical trials w...

Background. Antigen specific immunotherapy, in which autoantigen molecules or peptide epitopes thereof are delivered into patients to promote immune tolerance, is an attractive approach to the treatment of antigen specific autoimmune diseases as it provides a potential means of slowing disease progr...

Background: Cross-sectional data from the Type 1 Diabetes Exchange (T1DX) has shown that 1/3 of individuals with longstanding T1D maintain detectable C-peptide. Yet, no clear relationship between clinical or physiologic outcomes and level of C-peptide was identified. Therefore, the present study was...

Background. In type 1 diabetes (T1D), insulin-producing pancreatic β cells are destroyed by CD4+ and CD8+ autoreactive T cells. Antigen-specific tolerance is desirable for T1D immunotherapy to avoid generalised immunosuppression. Our vaccine strategy uses liposome nanocarriers encapsulating disease...

BACKGROUND: The importance of gut bacteria in human physiology, immune regulation and disease pathogenesis is well established. In contrast, the composition and dynamics of the gut virome (the viral component of the microbiome) remain largely unknown in adults including pregnant women. Viruses are i...

Engineering Erythrocytes for Immune Tolerance via CellSqueeze® Technology Derrick P. McCarthy1, Maria E. Trujillo1, Amritha Ramakrishnan1, Lindsay J. Moore1, Alfonso V. Suarez1, Finola E. Moore1, Howard Bernstein1, Armon Sharei1 SQZ Biotechnologies, 134 Coolidge Avenue, Watertown, Massachussetts, 0...

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 EXALT program (FP7 EU grant) started off in February 2014. In addition to an extensive preclinical research plan, the final objective of the project is to perform a phase I clinical trial in recent-onset (≤ 6 months) adult T1D patients, using an immunotherapeutic preparation, called ImotopeTM...

Background: Children with Down’s syndrome (DS) are at increased risk of islet, gut and thyroid autoimmunity. Onset of diabetes is accelerated in children with DS compared with the general population with 22% diagnosed before the age of 2 years. In addition, children with DS and diabetes have less ...

  Background   In TEDDY fish-derived fatty acid status during childhood was inversely associated with the risk of islet autoimmunity (IA). The current study aimed to examine the association of fish consumption with the risk of IA as well as IAA only and GADA only as the first appearing autoantibod...

  BACKGROUND: Analysis of autoantigen-specific CD4+ T cells is key for the understanding of T1D pathogenesis. To meet the dual challenge of understanding the frequency of such cells in different cellular compartments and their antigen experience, we developed an approach that combines T cell recept...

Background: Two transgenic NOD mouse models, the NOD-PerIg and the 116C-NOD, were generated and characterized to better understand the role of B cells in the development of T1D. The NOD-PerIg model expresses an immunoglobulin of naturally occurring islet-infiltrating B-lymphocyte (IIBLs) in NOD mice...

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...

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...

A recent proof of concept phase II trial demonstrated prevention of C-peptide decline in newly-diagnosed patients with type 1 diabetes (T1D) through administration of the drug Abatacept by intravenous infusion. Abatacept blocks the CD80/CD86 co-stimulation pathway, upon which lymphocytes are depende...

Background. Peptide immunotherapy aims to induce the tolerance to beta-cell antigens and stop beta-cell destruction in Type 1 diabetes (T1D). Proinsulin peptide C19-A3 is safe and potentially effective in modulating autoreactive CD4+ T-cells and preserving beta-cell function. Methods. Our aim is to ...

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:...

Physical exercise preserves beta cell function in humans with type 2 diabetes. Exercise also reduces insulitis and preserves beta cell function in the NOD mouse model of type 1 diabetes (T1D). We hypothesised that exercise will also preserve beta-cell function in humans with T1D, and undertook a pil...

Changes in the gut microbiota have been implicated in the pathogenesis of type 1 diabetes (T1D). The causes and functional consequences of an altered microbiota to the host immune response against the pancreas in T1D is unknown. We have performed a multi-omic integrative analyses of human stool samp...

Background: FOXP3-positive regulatory T cells (Tregs) are important for maintaining peripheral immune tolerance. Multiple lines of evidence suggest that the dysfunction of Tregs plays a key role in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D). However, previous studies a...

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: 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...

BACKGROUND: Epidemiological research and studies on patient samples have indicated that enterovirus infections, especially the ones caused by Coxsackieviruses (CVB) are connected to type 1 diabetes (T1D). We have hypothesized that CVB infections predispose genetically susceptible individuals to T1D ...

Molecular mechanisms triggering the onset of islet autoimmunity and progression to clinically overt type 1 diabetes (T1D) remain poorly understood. microRNAs (miRNAs) critically regulate immune homeostasis. While profiles of total miRNA abundance in T-cells have been reported previously, none have ...

  Background T1D natural history follow-up studies starting from birth have shown that usually either IAA or GADA is the first appearing islet autoantibody. Children different for these two forms differ also in autoimmunity process-associated genetic markers and distribution of seroconversion age,...

In mice, immune responses to antigen administered in the absence of adjuvant are typically tolerogenic through the induction of regulatory T cells (Treg) and the deletion/inactivation of conventional T cells (Tconv). Nevertheless, antigen-specific immunotherapy (ASI) approaches in autoimmune and al...

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:...

Islet antigen reactive memory CD4 (IARM-CD4) T cells contribute to the development of type 1 diabetes (T1D), and are detected in peripheral blood before and after diagnosis. We used a CD154 activation assay in conjunction with single cell RNAseq of IARM-CD4 T cells to identify novel characteristics ...

Background: Patients with brittle type 1 diabetes are more prone to extreme swings in blood glucose levels, resulting in frequent bouts of hyper- or hypo-glycemia. The intestinal microbiota plays an important role in regulating glucose homeostasis. We therefore investigated the effect of fecal micro...

  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...