Serum GAD65 antibody levels were not associated with any of the following groups: neurological disease, neurological disease and diabetes, diabetes only, no neurological diagnosis and no diabetes mellitus, or cancer.
A total of 31 Somali children ≤19 yr were treated for type 1 diabetes (T1D) at the University of Minnesota Masonic Children's Hospital and Children's Hospitals and Clinics of Minnesota underwent analysis of human leukocyte antigen (HLA) alleles (n = 30) and diabetes autoantibodies [glutamic acid decarboxylase (GAD65), islet antigen 2 (IA-2), zinc transporter 8 (ZnT8); n = 31].
Thirty-two Japanese children (eight males, 24 females) with type 1 diabetes negative for glutamate decarboxylase (GAD) 65 and/or IA-2A autoantibodies and who were aged >5 to 15.1 years at diagnosis were recruited from 16 independent hospitals participating in the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT).
The aims of our study were to explore the diabetes-preventive effect in NOD mice and the potential mechanisms of an optimized co-expression DNA vaccine containing GAD65 fragment gene with the IL-10 gene (SGAD65190-315 /IL-10).
Autoantibodies to GAD65(96-585) in relatives are more closely associated with diabetes risk than those to full-length GAD, suggesting that assays using N-terminally truncated GAD should be used to select participants for intervention trials.
Our results indicate that a single subcutaneous hindpaw inoculation of vectors expressing GAD65 or GAD67 reduced diabetes-induced mechanical allodynia to a degree that was greater than daily injections of gabapentin in rats.
Thirty four (19 males and 15 female) unrelated Japanese children with glutamate decarboxylase (GAD) 65 antibodies and/or IA-2A-negative T1D and diabetes diagnosed at < 5 yr of age were recruited from 17 unrelated hospitals participating in the Japanese Study Group of Insulin Therapy for children and adolescent diabetes (JSGIT).
Data were pooled from prospective cohort studies performed in Colorado (recruitment, 1993-2006), Finland (recruitment, 1994-2009), and Germany (recruitment, 1989-2006) examining children genetically at risk for type 1 diabetes for the development of insulin autoantibodies, glutamic acid decarboxylase 65 (GAD65) autoantibodies, insulinoma antigen 2 (IA2) autoantibodies, and diabetes.
The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC.
In summary, the presence of antigen experienced GAD65-specific T cells in the subjects with diabetes-associated autoimmunity is encouraging for further directions in the prediction of T1D.
In multivariable analysis, age ≤ 20 years (hazard ratio 2.13, P = 0.03), IA-2A (2.15, P = 0.005), IAA (1.73, P = 0.01), ICA (2.37, P = 0.002), and ZnT8A (1.87, P = 0.03) independently predicted diabetes, whereas HLA type (high and moderate vs. low risk) and GAD65A did not (P = 0.81 and 0.86, respectively).
The Diabetes Autoimmunity Study in the Young (DAISY) followed prospectively for development of persistent IA (autoantibodies to insulin, GAD65, IA-2, or ZnT8 on at least two consecutive exams) and diabetes 1715 non-Hispanic white children at increased genetic risk for T1D.
HLA-DQB1 genotypes and islet cell autoantibodies against GAD65 and IA-2 in relation to development of diabetes post partum in women with gestational diabetes mellitus.
Patients with interferon-associated type 1 diabetes retained higher levels of fasting serum C peptide as well as GAD65 antibodies than those with type 1A diabetes until 2 to 4 years after onset.
Our results show for the first time the occurrence of antigen-specific induced insulitis, impaired glucose homeostasis and diabetes after immunization with a clinically relevant, human autoantigen in the context of HLA-DQ8 diabetes-susceptibility transgenes and human GAD65 expression in beta-cells.
We report the development of antigen-specific insulitis in double-transgenic mice carrying the HLA-DQ8 diabetes-susceptibility haplotype and expressing the human autoantigen GAD65 in pancreatic beta-cells.
Examined here are current problems of definition including 'adaptive' and 'innate' types of autoimmunity, estimations of population burdens of autoimmune diseases, the nature of autoepitopes in the context of the diabetes autoantigen GAD65, and the complexities of immune tolerance and the genetic influences thereon, leading to the nomination of multiple 'tolerance/autoimmunity' genes as critical components of pathogenesis.
The Diabetes Prevention Trial-1 found 2817 ICA-positive relatives who were tested for biochemical autoantibodies (GAD65, ICA512, and insulin) and HLA-DQ haplotypes, and 2796 of them were followed up for progression to diabetes for up to 8 yr (median, 3.6 yr).
We provide evidence that a subgroup of ICAs predicts a more rapid progression to insulin-requiring diabetes in GAD65 and IA-2 AA-positive relatives and should remain part of the assessment of T1DM risk for intervention trials.
In healthy GAD65Ab-positive individuals who did not progress to diabetes during a 9-year follow-up period ( n=51), binding to GAD65-E517P was reduced by only 28% compared with binding to wild-type GAD65.