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
| العنوان: | 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 |
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| المؤلفون: | Kimberly Shafer-Weaver, John A. Todd, Lawrence F. Jerome, Jill White, Austin D. Swafford, Michael J. Lenardo, Conor A Callahan, Luba Rakhlin, Carrie L. Lucas, Reid von Borstel, Ping Jiang, Helen Stevens, Bernice Lo, Douglas R. Mathern, L. J. Davison |
| المساهمون: | Davison, Lucy [0000-0002-1920-0817], Apollo - University of Cambridge Repository |
| المصدر: | Journal of Translational Medicine, Vol 9, Iss 1, p 203 (2011) Journal of Translational Medicine |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | medicine.medical_treatment, Insulin Antibodies, lcsh:Medicine, 32 Biomedical and Clinical Sciences, Nod, Mice, Radioligand Assay, 0302 clinical medicine, electrochemiluminescence, Mice, Inbred NOD, Insulin-Secreting Cells, Electrochemistry, Medicine, 3202 Clinical Sciences, NOD mice, Medicine(all), 0303 health sciences, IAA, Diabetes, General Medicine, 3. Good health, human autoantibodies, Disease Progression, Female, Radiobinding assay, 4.2 Evaluation of markers and technologies, medicine.medical_specialty, insulin, 030209 endocrinology & metabolism, Autoimmune Disease, Sensitivity and Specificity, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Clinical Research, Diabetes mellitus, Internal medicine, Animals, Humans, Metabolic and endocrine, 030304 developmental biology, Autoantibodies, Type 1 diabetes, ECL, business.industry, IA, Biochemistry, Genetics and Molecular Biology(all), Insulin, Research, Prevention, lcsh:R, Autoantibody, Reproducibility of Results, medicine.disease, 4.1 Discovery and preclinical testing of markers and technologies, Endocrinology, Diabetes Mellitus, Type 1, ROC Curve, Immunology, Luminescent Measurements, business, 4 Detection, screening and diagnosis, Insulitis |
| الوصف: | Background The 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. Methods We 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. Results Our 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. Conclusions These 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. |
| وصف الملف: | text/xml; application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd8b0a7e06c0ba6d78821da7d356e4a0Test https://ora.ox.ac.uk/objects/uuid:10f676da-4c07-48a1-9ce2-9b8443723859Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dd8b0a7e06c0ba6d78821da7d356e4a0 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |