A5035095598- Diabetes and associated disorders
- Pancreatic function and diabetes
- Diabetes Management and Research
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Celiac Disease Research and Management
- Monoclonal and Polyclonal Antibodies Research
- Adrenal Hormones and Disorders
- Diabetes Treatment and Management
- Neuroendocrine Tumor Research Advances
- CAR-T cell therapy research
- Diet and metabolism studies
- Hormonal Regulation and Hypertension
- Diet, Metabolism, and Disease
- COVID-19 Clinical Research Studies
- Adipose Tissue and Metabolism
- Nuclear Structure and Function
- Pancreatic and Hepatic Oncology Research
- Immunodeficiency and Autoimmune Disorders
- Drug-Induced Adverse Reactions
- Pituitary Gland Disorders and Treatments
- SARS-CoV-2 and COVID-19 Research
- Chronic Myeloid Leukemia Treatments
- Biotin and Related Studies
University of Colorado Denver
2016-2025
University of Colorado Anschutz Medical Campus
2014-2025
The Medical Center of Aurora
2019-2024
Diabetes Australia
2014-2022
University of Colorado Health
2020
University Hospital Münster
2019
University of Colorado Boulder
2014
Few studies have assessed factors associated with severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) in adults type 1 diabetes (T1D).Our objective was to determine frequency of the occurrence SH DKA T1D.We conducted a cross-sectional analysis from T1D Exchange clinic registry at 70 U.S. endocrinology centers.Analysis included 7012 participants aged 26 93 years old for ≥2 years.Higher frequencies were lower socioeconomic status (P < .001). strongly duration .001), 18.6% those ≥40 having...
Type 1 diabetes results from chronic autoimmune destruction of insulin-producing β-cells within pancreatic islets. Although insulin is a critical self-antigen in animal models diabetes, due to extremely limited access pancreas samples, little known about human antigenic targets for islet-infiltrating T cells. Here we show that proinsulin peptides are targeted by cells patients with type diabetes. We identified hundreds inflamed islets three young organ donors short disease duration high-risk...
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 diagnosis. Based human and preclinical studies, we hypothesized that a combination low-dose anti-thymocyte globulin (ATG) pegylated granulocyte CSF (G-CSF) would patients established T1D (duration >4 months <2 years).A randomized, single-blinded, placebo-controlled trial was performed 25 subjects: 17 subjects...
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 no consensus on relative importance various positions or “registers” this can take when bound in groove NOD MHCII molecule, IA g7 . This has hindered structural studies and tracking relevant cells vivo with fluorescent peptide-MHCII tetramers. Using mutated B:9–23 peptides methods trapping particular registers, we show that most, if...
Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αβTCR is identified from cytotoxic lymphocytes of with carbamazepine-SJS/TEN, its expression showing drug/phenotype-specificity an bias for HLA-B*15:02. This has binding affinity carbamazepine...
BackgroundType 1 diabetes results from autoimmune-mediated destruction of β cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, preclinical studies show that it reverses prevents diabetes. Our aim was to evaluate the safety efficacy in preserving β-cell function patients with recent-onset type diabetes.MethodsWe did a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients (<100 days diagnosis), aged 18–45...
We recently established that hybrid insulin peptides (HIPs) are present in human islets and T cells reactive to HIPs found the residual of organ donors with type 1 diabetes (T1D). Here, we investigate whether HIP-reactive indicative ongoing autoimmunity patients T1D. used interferon-γ enzyme-linked immune absorbent spot analyses on peripheral blood mononuclear (PBMCs) determine new-onset T1D or control subjects displayed T-cell reactivity a panel 16 HIPs. observed nearly one-half responded...
Significance Insulin is a major self-antigen in type 1 diabetes (T1D), and as such, insulin-based immunotherapies have been trialed to treat the underlying autoimmunity but with minimal clinical benefit. Here, we comprehensively assessed reactivity insulin its precursor, preproinsulin, by CD8 T cells obtained from pancreatic islets of organ donors without T1D. highly reactive peptides throughout entire preproinsulin protein were only found T1D at varying frequencies. Our results suggest...
The ability to alter antigen specificity by T-cell receptor (TCR) or chimeric (CAR) gene transfer has facilitated personalized cellular immune therapies in cancer. Inversely, this approach can be harnessed autoimmune settings attenuate inflammation redirecting the of regulatory T cells (Tregs). Herein, we demonstrate efficient protocols for lentiviral TCRs that recognize type 1 diabetes-related autoantigens with goal tissue-targeted induction antigen-specific tolerance halt β-cell...
Significance Certain class II major histocompatibility alleles confer disease risk for type 1 diabetes (T1D). Insulin-specific and other autoantibodies often precede T1D development, but efforts at prevention using insulin preparations (subcutaneous, oral, intranasal) to induce tolerance have not been effective. Measuring insulin-specific T-cell responses from the peripheral blood has a challenging feat would allow assessment of therapeutic response in these trials. In our study, we report...
OBJECTIVE To evaluate the contemporary prevalence of diabetic peripheral neuropathy (DPN) in participants with type 1 diabetes T1D Exchange Clinic Registry throughout U.S. RESEARCH DESIGN AND METHODS DPN was assessed Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) adults ≥5 years duration. A score ≥4 defined DPN. Associations demographic, clinical, and laboratory factors were assessed. RESULTS Among 5,936 (mean ± SD age 39 18 years, median duration [interquartile range 11,...
Type 1 diabetes results from an autoimmune attack directed at pancreatic beta cells predominantly mediated by T cells. Transplantation of stem cell derived beta-like (sBC) have been shown to rescue in preclinical animal models. However, how sBC will respond inflammatory environment with diabetogenic a strict human setting has not determined. This is due the lack model systems that closely recapitulates T1D. Here, we present reliable vitro assay measure autologous CD8 stimulation against...
Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion immune-mediated pathology, biomarkers such autoantibodies are generally lacking. Here, we used unbiased proteome-wide screening approach to identify the adipocyte-specific lipid droplet protein perilipin 1 (PLIN1) in a murine model autoimmune polyendocrine syndrome type (APS1). We then tested for PLIN1 human subjects with acquired two independent severe breaks immune tolerance...
Abstract Class II major histocompatibility molecules are the primary susceptibility locus for many autoimmune disorders, including type 1 diabetes. Human DQ8 and I-Ag7, in NOD mouse model of spontaneous diabetes, confers diabetes risk by modulating presentation specific islet peptides thymus periphery. We used an silico molecular docking program to screen a large “druglike” chemical library define small capable occupying structural pockets along I-Ag7 binding groove, with objective...