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In the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), an insulin peptide (B:9-23) is a major target for pathogenic CD4(+) T cells. However, there is no consensus on the relative importance of the various positions or "registers" this peptide can take when bound in the groove of the NOD MHCII molecule, IA(g7). This has hindered structural(More)
The autoimmune polyglandular syndromes-a group of syndromes comprising a combination of endocrine and nonendocrine autoimmune diseases-differ in their component diseases and in the immunologic features of their pathogenesis. One of the three main syndromes, type 1 autoimmune polyglandular syndrome (APS-1), has a unique pathogenic mechanism owing to(More)
CONTEXT Recent studies have implicated proinflammatory responses in the mechanism of type 1 diabetes (T1D). OBJECTIVE Our objective was to evaluate the safety and effects of therapy with the anti-inflammatory serum protein α1-antitrypsin (AAT) on islet function and innate immunity in recent-onset patients. DESIGN AND SETTING This was an open-label phase(More)
CONTEXT Few studies have assessed factors associated with severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D). OBJECTIVE Our objective was to determine frequency of and factors associated with the occurrence of SH and DKA in adults with T1D. DESIGN AND SETTING We conducted a cross-sectional analysis from the T1D(More)
Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA-like molecules determining tissue-specific targeting that, with the loss of tolerance, leads to organ-specific autoimmunity. Disorders such as type 1A diabetes, Graves disease, Hashimoto thyroiditis, Addison disease, and(More)
AIMS/HYPOTHESIS Type 1 diabetes results from a chronic autoimmune process continuing for years after presentation. We tested whether treatment with teplizumab (a Fc receptor non-binding anti-CD3 monoclonal antibody), after the new-onset period, affects the decline in C-peptide production in individuals with type 1 diabetes. METHODS In a randomised(More)
The insulin peptide B:9-23 is a natural antigen in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). In addition to αβ T cells and B cells, γδ T cells recognize the peptide and infiltrate the pancreatic islets where the peptide is produced within β cells. The peptide contains a cysteine in position 19 (Cys19), which is required for the γδ(More)
BACKGROUND Previous efforts to preserve β cell function in individuals with type 1 diabetes (T1D) have focused largely on the use of single immunomodulatory agents administered within 100 days of diagnosis. Based on human and preclinical studies, we hypothesized that a combination of low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte CSF(More)
PURPOSE OF REVIEW Description of the immunologic components needed for autoimmune diabetes. RECENT FINDINGS The major histocompatability complex (MHC) class II molecules are the primary susceptibility genes for many autoimmune diseases, including type 1 diabetes. Understanding of the structural interaction between MHC molecules, antigenic peptides, and(More)
Type 1 diabetes (T1D) is a chronic autoimmune disease that results in the specific immune destruction of insulin producing beta cells. Currently there is no cure for T1D and treatment for the disease consists of lifelong administration of insulin. Immunotherapies aimed at preventing beta cell destruction in T1D patients with residual c-peptide or in(More)