Abstract and Introduction
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.
Islet autoantibodies play an essential role in the prediction of type 1 diabetes (T1D). These autoantibodies can appear as early as 6–9 months of age and usually precede clinical diabetes by years. Accurate detection of islet autoantibodies is crucial for finding the environmental factors that may trigger islet autoimmunity and promote progression to T1D.
In addition, islet autoantibodies are used extensively to stage diabetes risk and as the inclusion criteria for trials to prevent T1D. The risk of developing T1D is strongly associated with the number of islet autoantibodies among both first-degree relatives of patients with T1D and general population subjects. Children who have two or more persistent islet autoantibodies are at high risk; 70% of them will progress to diabetes in <10 years. In contrast, children with a single positive persistent autoantibody are at a much lower risk, with <10% progressing to diabetes in 10 years. Further stratification of these single autoantibodies for disease relevance by more-specific assays would greatly enhance staging of diabetes risk for clinical trials.
We recently developed an electrochemiluminescence (ECL) insulin autoantibody (IAA) assay that has been shown to be more sensitive and more specific for detecting diabetes than the standard micro-IAA radioassay. In the current study, we evaluated a similar ECL-GAD antibody (GADA) assay and compared its sensitivity and disease relevance among GADA-positive children by the standard GADA radioassay.