We examined the frequency and phenotype of circulating preproinsulin (PPI)-specific and insulin B (InsB)-specific CD8<sup>+</sup> T cells in HLA-B*3906<sup>+</sup> children newly diagnosed with T1D and in high-risk HLA-A*2402<sup>+</sup> children before the appearance of disease-specific autoantibodies and before diagnosis of T1D.
Identification of Novel T1D Risk Loci and Their Association With Age and Islet Function at Diagnosis in Autoantibody-Positive T1D Individuals: Based on a Two-Stage Genome-Wide Association Study.
Together, these results provide a better characterization of antisense targets in INS primary transcripts for restorative strategies designed to improve the INS splicing defect associated with type 1 diabetes.
Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes.
Consistent with prior reports, unmethylated INS DNA values correlated with methylated INS DNA values, which were also elevated among T1D subjects (P < 0.001).
Genotypic risk score for type 1 diabetes was inversely associated with detectable C-peptide secretion: the most strongly associated loci were the HLA and INS gene regions.
We explored the prevalence of the following autoimmune disorders: insulin-dependent diabetes mellitus [IDDM], psoriasis, Sjögren syndrome, coeliac disease, systemic lupus erythematosus [SLE], primary sclerosis cholangitis [PSC] and autoimmune thyroiditis, among all IBD patients vs non-IBD controls.
Surprisingly, although responses to each of these peptides can be readily detected after in vitro expansion, our results indicated that only proinsulin specific T cells were consistently detectable at moderate frequencies in subjects with T1D.
In type 1 diabetes (T1D), proinsulin is a major autoantigen and the insulin B:9-23 peptide contains epitopes for CD4<sup>+</sup> T cells in both mice and humans.
C-peptide and proinsulin were measured in fasting and stimulated sera from 319 subjects with long-standing type 1 diabetes (≥3 years) and 12 control subjects without diabetes.
HLA-DR3-DQ2<sup>+</sup>huCD4<sup>+</sup>IA/IE<sup>-/-</sup>RIP.B7.1<sup>+</sup> mice spontaneously developed autoimmune diabetes (incidence 46% by 35 weeks of age), accompanied by numerous hallmarks of human type 1 diabetes (autoantibodies against GAD65 and proinsulin; pancreatic islet infiltration by CD4<sup>+</sup>, CD8<sup>+</sup> B220<sup>+</sup>, CD11b<sup>+</sup> and CD11c<sup>+</sup> immune cells).
Laser capture microdissection followed by mass spectrometry revealed reductions in the proinsulin processing enzymes prohormone convertase 1/3 (PC1/3) and carboxypeptidase E (CPE) in T1D donors.
The aim of this meta-analysis was to determine the association of common type 1 diabetes (T1D) and type 2 diabetes (T2D) gene variants (protein tyrosine phosphatase non-receptor 22 [PTPN22] rs2476601C/T, insulin [INS] rs689A/T and transcription factor 7-like 2 [TCF7L2] rs7903146C/T) with latent autoimmune diabetes in adults (LADA).
The abundance of circulating insulin gene promotor cell-free DNA (INS cfDNA) was shown to be valuable as a predictive biomarker of β-cell death in individuals with Type 1 diabetes (T1D) as well as with gestational diabetes.
Here, we analysed the effect of T1D-associated major HLA class II haplotypes and seven single nucleotide polymorphisms in six non-HLA genes [INS (rs689), PTPN22 (rs2476601), IL2RA (rs12722495 and rs2104286), PTPN2 (rs45450798), CTLA4 (rs3087243) and ERBB3 (rs2292239)] on peripheral blood Treg frequencies.
In this work, iron oxide NPs are surface-engineered for the copackaging of the autoantigen proinsulin, a major target of adaptive immunity in type 1 diabetes (T1D), and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methylester (ITE), a small drug conditioning a tolerogenic environment.
A LIPS assay using the NL-proinsulin fusion protein was developed and compared to radioimmunoassay (RIPA) in testing sera from 50 healthy controls and 34 T1D patients.