title: GAD65 autoantibodies detected by electrochemiluminescence assay identify high risk for type 1 diabetes.
abstract: The identification of diabetes-relevant islet autoantibodies is essential for predicting and preventing type 1 diabetes (T1D). The aim of the current study was to evaluate a newly developed electrochemiluminescence (ECL)-GAD antibody (GADA) assay and compare its sensitivity and disease relevance with standard radioassay. The assay was validated with serum samples from 227 newly diagnosed diabetic children; 68 prediabetic children who were prospectively followed to T1D; 130 nondiabetic children with confirmed islet autoantibodies to insulin, GAD65, IA-2, and/or ZnT8 longitudinally followed for 12 ± 3.7 years; and 181 age-matched, healthy, antibody-negative children. The ECL-GADA assay had a sensitivity similar to that of the standard GADA radioassay in children newly diagnosed with T1D, prediabetic children, and high-risk children with multiple positive islet autoantibodies. On the other hand, only 9 of 39 nondiabetic children with only a single islet autoantibody (GADA only) by radioassay were positive for ECL-GADA. GADA not detectable by ECL assay is shown to be of low affinity and likely not predictive of future diabetes. In conclusion, the new ECL assay identifies disease-relevant GADA by radioassay. It may help to improve the prediction and correct diagnosis of T1D among subjects positive only for GADA and no other islet autoantibodies.
authors: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado.
authors: Dongmei
authors: D
authors: Miao
authors: K Michelle
authors: KM
authors: Guyer
authors: Fran
authors: F
authors: Dong
authors: Ling
authors: L
authors: Jiang
authors: Andrea K
authors: AK
authors: Steck
authors: Marian
authors: M
authors: Rewers
authors: George S
authors: GS
authors: Eisenbarth
authors: Liping
authors: L
authors: Yu
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007223:Infant; D049449:Luminescence; D008297:Male; D011236:Prediabetic State / Q000175:diagnosis* / Q000276:immunology; D012306:Risk; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
references: Diabetes. 2007 Jun;56(6):1527-33
references: 17325256
references: Diabetes. 1996 Jul;45(7):926-33
references: 8666144
references: J Clin Endocrinol Metab. 1996 Dec;81(12):4264-7
references: 8954025
references: Clin Exp Immunol. 2012 Jan;167(1):67-72
references: 22132886
references: Diabetes. 1997 Nov;46(11):1701-10
references: 9356015
references: J Clin Endocrinol Metab. 2010 Jul;95(7):3360-7
references: 20444913
references: Diabetes Metab Res Rev. 2009 Oct;25(7):615-22
references: 19637309
references: Diabetes Care. 2013 Aug;36(8):2266-70
references: 23423694
references: J Clin Invest. 2004 Aug;114(4):589-97
references: 15314696
references: JAMA. 2013 Jun 19;309(23):2473-9
references: 23780460
references: Diabetes. 1999 Jan;48(1):170-5
references: 9892239
references: Diabetes. 2012 Jan;61(1):179-86
references: 22124462
references: Diabetes Care. 2009 Dec;32(12):2269-74
references: 19741189