Objective
We will reexam all the islet autoantibodies (IAbs) with a new electrochemiluminescence (ECL) assay in T1D high-risk participants of the TEDDY study at the Colorado site. The ECL IAb data will be compared with the existing IAb data by the standard radio binding assay (RBA) used in TEDDY study to: 1. Exam the timing when the first IAb appears; 2. Compare how well each of the four IAbs (IAA, GADA, IA-2A, and ZnT8A) detected by ECL or RBA assay predicts clinical T1D onset.
Background Rationale
The Environmental Determinants of Diabetes in the Young (TEDDY) study, set up by the National Institutes of Health, aims to find environmental factors that either increase the risk of or protect against developing islet autoimmunity and type 1 diabetes (T1D). For this study to work well, it needs accurate tests to detect truly positive signals at the time when people develop islet autoantibodies (IAbs)at the very beginning. The current test, the radio-binding assay (RBA), is widely used but has some challenges, such as not detecting IAbs early enough, not being specific enough for predicting the disease, and being costly. A newer test, the electrochemiluminescence (ECL) assay, has shown better sensitivity, more accurate disease prediction, and more cost-efficiency in various T1D studies.
Description of Project
Background: The Environmental Determinants of Diabetes in the Young (TEDDY) study, set up by the National Institutes of Health, aims to find environmental factors that either increase the risk of or protect against developing islet autoimmunity and type 1 diabetes (T1D). For this study to work well, it needs accurate tools to detect truly signals at the time when people develop islet autoantibodies (IAbs) at the very beginning. The current test, the radio-binding assay (RBA), is widely used but has some challenges, such as not detecting IAbs early enough, not being specific enough for predicting the disease, and being costly. A newer test, the electrochemiluminescence (ECL) assay, has shown better sensitivity, accurate disease prediction, and more cost-efficiency.
Objective: In this proposal, we will compare data of IAb analysis by RBA with ECL assay in T1D high-risk participants from the TEDDY study to: 1. Exam the timing when IAbs first appear using the ECL assay and compare it with the RBA. 2. Compare how well each of the four IAbs (IAA, GADA, IA-2A, and ZnT8A) detected by ECL or RBA assay predicts clinical T1D onset.
Approaches: We plan to remeasure all four IAbs (IAA, GADA, IA-2A, and ZnT8A) using the ECL assay in all participants from the Colorado site of the TEDDY study who tested positive for one or more IAbs, as well as in 300 participants who tested negative for all IAbs. The ECL assay results will be compared with the RBA results to exam the timing when the first positive seroconversion happens and how well each assay predicts the disease.
Anticipated Outcomes: We expect that in T1D high-risk participants from the TEDDY study, the ECL assays will: 1. Detect IAbs earlier than the RBA, pinpointing the time more precisely when the first IAb appears. 2. Improve accuracy for T1D prediction by distinguishing real disease-related from non-disease relevant IAbs.
Significance: The large, closely monitored participants in the TEDDY study provides a unique chance to validate and compare the sensitivity and disease specificity of the IAb assays. This proposal's data will validate our previous study that the ECL assay offers higher sensitivity and higher disease specificity. This study will help the future population-based screenings for T1D, improving disease prediction, allowing earlier detection, and enhancing screening efficiency with high throughput and low cost.
Anticipated Outcome
We expect that in high-risk participants for type 1 diabetes from the TEDDY study, the electrochemiluminescence assays will: 1. Detect islet autoimmunity earlier than the radio binding assay, providing the more accurate timing when the appearance of the first islet autoantibody occurs. 2. Improve accuracy for T1D prediction by distinguishing real disease-related from non-disease relevant islet autoantibodies.
Relevance to T1D
The large, closely monitored participants in the TEDDY study provides a unique chance to validate and compare the sensitivity and disease specificity of the islet autoantibody assays. This proposal's data will confirm our previous finding that the multiplex ECL assay is a more efficient tool for type 1 diabetes screening, offering higher sensitivity and higher disease specificity. This study will help in future population-based screenings for type 1 diabetes, improving disease prediction, allowing earlier detection, and enhancing screening efficiency with high throughput and low cost.