ArticleJournal of translational medicine2011
Antibodies against insulin measured by electrochemiluminescence predicts insulitis severity and disease onset in non-obese diabetic mice and can distinguish human type 1 diabetes status.
Article in Journal of translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 25 citations in OpenAlex.
- Polyfunctional T follicular helper cells drive checkpoint-inhibitor diabetes and are targeted by JAK inhibitor therapy.JCI insight · 2025Article
- RANKL/RANK is required for cytokine-induced beta cell death; osteoprotegerin, a RANKL inhibitor, reverses rodent type 1 diabetes.Science advances · 2023Article
- Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen-specific CD4 T cells.Science translational medicine · 2023Article
- Tolerogenic Immune-Modifying Nanoparticles Encapsulating Multiple Recombinant Pancreatic β Cell Proteins Prevent Onset and Progression of Type 1 Diabetes in Nonobese Diabetic Mice.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Contrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis in mouse models of type1 diabetes.Nature communications · 2020Article
- Type 1 diabetes pathogenesis and the role of inhibitory receptors in islet tolerance.Annals of the New York Academy of Sciences · 2020Review
- Amelioration of Autoimmune Diabetes of NOD Mice by Immunomodulating Probiotics.Frontiers in immunology · 2020Article
- Metabolically inactive insulin analogue does not prevent autoimmune diabetes in NOD mice.Diabetologia · 2017Article
- Loss of immune tolerance to IL-2 in type 1 diabetes.Nature communications · 2016Article
- The p. N103K mutation of leptin (LEP) gene and severe early onset obesity in Pakistan.Biological research · 2016Observational
- Novel diagnostic and therapeutic approaches for autoimmune diabetes--a prime time to treat insulitis as a disease.Clinical immunology (Orlando, Fla.) · 2015Review
- Autoimmunity against INS-IGF2 protein expressed in human pancreatic islets.The Journal of biological chemistry · 2013Article
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15 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThe detection of insulin autoantibodies (IAA) aids in the prediction of autoimmune diabetes development. However, the long-standing, gold standard 125I-insulin radiobinding assay (RBA) has low reproducibility between laboratories, long sample processing times and requires the use of newly synthesized radiolabeled insulin for each set of assays. Therefore, a rapid, non-radioactive, and reproducible assay is highly desirable.
methodsWe have developed electrochemiluminescence (ECL)-based assays that fulfill these criteria in the measurement of IAA and anti-insulin antibodies (IA) in non-obese diabetic (NOD) mice and in type 1 diabetic individuals, respectively. Using the murine IAA ECL assay, we examined the correlation between IAA, histopathological insulitis, and blood glucose in a cohort of female NOD mice from 4 up to 36 weeks of age. We developed a human IA ECL assay that we compared to conventional RBA and validated using samples from 34 diabetic and 59 non-diabetic individuals in three independent laboratories.
resultsOur ECL assays were rapid and sensitive with a broad dynamic range and low background. In the NOD mouse model, IAA levels measured by ECL were positively correlated with insulitis severity, and the values measured at 8-10 weeks of age were predictive of diabetes onset. Using human serum and plasma samples, our IA ECL assay yielded reproducible and accurate results with an average sensitivity of 84% at 95% specificity with no statistically significant difference between laboratories.
conclusionsThese novel, non-radioactive ECL-based assays should facilitate reliable and fast detection of antibodies to insulin and its precursors sera and plasma in a standardized manner between laboratories in both research and clinical settings. Our next step is to evaluate the human IA assay in the detection of IAA in prediabetic subjects or those at risk of type 1 diabetes and to develop similar assays for other autoantibodies that together are predictive for the diagnosis of this common disorder, in order to improve prediction and facilitate future therapeutic trials.
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