Abstract
Islet autoantibodies are predominantly measured by radioassay to facilitate risk assessment and diagnosis of type 1 diabetes. However, the reliance on radioactive components, large sample volumes and limited throughput renders radioassay testing costly and challenging. We developed a multiplex analysis platform based on antibody detection by agglutination-PCR (ADAP) for the sample-sparing measurement of GAD, IA-2 and insulin autoantibodies/antibodies in 1 μL serum. The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. The average overall agreement between ADAP and radioassay was above 91%. The average clinical sensitivity and specificity were 96% and 97%. In the IASP 2018 workshop, ADAP achieved the highest sensitivity of all assays tested at 95% specificity (AS95) rating for GAD and IA-2 autoantibodies and top-tier performance for insulin autoantibodies. Furthermore, ADAP correctly identified 95% high-risk individuals with two or more autoantibodies by radioassay amongst 39 relatives of T1D patients tested. In conclusion, the new ADAP assay can reliably detect the three cardinal islet autoantibodies/antibodies in 1μL serum with high sensitivity. This novel assay may improve pediatric testing compliance and facilitate easier community-wide screening for islet autoantibodies.
Highlights
Type 1 diabetes (T1D) is a chronic autoimmune disease, characterized by progressive destruction of pancreatic islet beta cells
The antibody detection by agglutinationPCR (ADAP) assay is capable of measuring antibodies against islet antigens
Islet-cell immunoassays remain the technological fulcrum for efforts to diagnose and predict autoimmune diabetes
Summary
Type 1 diabetes (T1D) is a chronic autoimmune disease, characterized by progressive destruction of pancreatic islet beta cells. T1D affects millions of Americans, with over 70,000 new cases arising each year. Over the past 20 years, the number of reported cases of T1D has doubled due to the global increase in incidence rate [1]. The presence of two or more islet autoantibodies defines the earliest stage of T1D [3]. Identification of these Stage 1 individuals reduces the risk of DKA by permitting timely glycemic control, and facilitates enrollment in clinical trials during a critical window when patients still harbor islet cell function and are more likely to respond favorably to immunomodulatory intervention [4]
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