Design and Measurement of Nonislet-Specific Autoantibodies for the Type 1 Diabetes Genetics Consortium Autoantibody...

The Type 1 Diabetes Genetics Consortium (T1DGC) comprised groups of investigators from many countries throughout the world, with a common goal of identifying genes predisposing to type 1 diabetes. The T1DGC ascertained and collected samples from families with two or more affected siblings with type 1 diabetes and generated a broad array of clinical, genetic, and immunologic data. The T1DGC Autoantibody Workshop was designed to distribute data for analyses to discover genes associated with autoantibodies in those with type 1 diabetes. In the T1DGC-affected sibling pair families, three T1DGC Network laboratories measured antibodies to the islet autoantigens GAD65 and the intracellular portion of protein tyrosine phosphatase (IA-2A). The availability of extensive genetic data provided an opportunity to investigate the associations between type 1 diabetes and other autoimmune diseases for which autoantibodies could be measured. Measurements of additional nonislet autoantibodies, including thyroid peroxidase, tissue transglutaminase, 21-hydroxylase, and the potassium/hydrogen ion transporter H+/K+-ATPase, were performed by the T1DGC laboratory at the Barbara Davis Center for Childhood Diabetes, Aurora, CO. Measurements of all autoantibodies were transmitted to the T1DGC Coordinating Center, and the data were made available to members of the T1DGC Autoantibody Working Groups for analysis in conjunction with existing T1DGC genetic data. This article describes the design of the T1DGC Autoantibody Workshop and the quality-control procedures to maintain and monitor the performance of each laboratory and provides the quality-control results for the nonislet autoantibody measurements.