Multiplex Microarray for the Detection of Pre-Type 1 Diabetes Autoantibodies

DESCRIPTION (provided by applicant): This SBIR project addresses an important medical need for improved, new technology-based assays for detecting auto antibodies relevant to Type I Diabetes (T1D). T1D affects a million Americans and its incidence is increasing at an alarming rate of 2 to 5% per year. In T1D, circulating auto antibodies against islet cell antigens reflect the process of autoimmune destruction of the insulin-producing beta-cells. Auto antibodies are clinically useful because they are present early in the autoimmune process, often years before patients develop hyperglycemia, and can be used as markers to identify individuals at risk for T1D and to predict risk, particularly when auto antibodies against multiple antigens, are present. Current assays, based on radio immuno adsorbant (RIA) or enzyme linked immunoadsorbant assays (ELISA) methods test for one antibody per assay and are cumbersome, expensive, and some have poor inter-laboratory reproducibility. New intervention strategies for T1D prevention depend on early detection of pre-T1D and sensitive and reliable analytical techniques are crucial. In Phase I, we will test the feasibility of a new multiplex microarray assay based on a novel colloid technology. A microarray format immunoassay will be developed for auto-anti-insulin (IAA), anti- insulinoma associated antigen ( IA-2) and anti-glutamic acid decarboxylase (GAD65)-three autoantibodies informative for T1D. The individual microarray assays will be multiplexed and the multiplex microarray assay performance evaluated relative to current RIA and ELISA assays. We will then evaluate the multiplex microarray assay performance using 25 reference samples. Results of Phase I will demonstrate the feasibility of the novel colloid multiplex micorarray technology as a platform for supporting assays to detect autoantibodies in T1D, and lay the groundwork for full scale development and clinical testing of an efficient, accurate, and reliable T1D clinical diagnostic assay in Phase II. 7. Project Narrative Prediction of T1D through autoantibody testing is critical for the proper identification of individuals at-risk for developing this disease. In T1D, despite the higher risk in relatives, 90% of new cases are sporadic cases occurring in individuals with no prior family history. Thus, in the absence of the capability to screen populations at large, most individuals at risk for T1D are not identified. Clearly, new assays with a better cost-benefit profile are needed to expand the benefit of autoantibody testing. The proposed multiplex microarray methodology is a practical, efficient system to test for T1D autoantibodies. This should allow for the identification of at risk individuals and thus provide a valuable resource for T1D prevention studies.