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Aims The TEDDY study seeks to identify environmental factors influencing the development of type 1 diabetes (T1D) using intensive follow-up of children at elevated genetic risk. The study requires a cost-effective yet accurate screening strategy to identify the high-risk cohort. Methods The TEDDY cohort was identified through newborn screening using HLA class II genes based on criteria established with pre-TEDDY data. HLA typing was completed at six international centers using different genotyping methods that can achieve >98% accuracy. Results TEDDY developed separate inclusion criteria for the general population (GP) and first degree relatives (FDR) of T1D patients. The FDR eligibility includes nine haplogenotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4b, DR4/1, DR4/13, DR4/9 and DR3/9) for broad HLA diversity, while the GP eligibility includes only the first four haplogenotypes with DRB1*0403 as an exclusion allele. TEDDY has screened 414,714 GP infants, of which 19,906 (4.8%) were eligible, while 1,415 of the 6,333 screened FDR infants (22.2%) were eligible. High resolution confirmation testing of the eligible subjects indicated that the low-cost and low-resolution genotyping techniques employed at the screening centers yielded an accuracy of 99%. There were considerable variations in eligibility rates among the centers for GP (3.5% – 7.4%) and FDR (19% – 32%) subjects. The eligibility rates among US ethnic groups were 0.9%, 1.3%, 5.0% and 6.9% for Asians, Black, Caucasians and Hispanics, respectively. Conclusions Different low-cost and low-resolution genotyping methods are useful for the efficient and accurate identification of a high-risk cohort for follow-up based on the TEDDY HLA inclusion criteria (ClinicalTrials.gov NCT00279318).

Calibration of flow cytometers is becoming an increasingly important issue for both quality control of instrument performance and quantitation of antibody binding capacity of cells. Due to the numerous different instruments and analysis software currently available, a standardized method of calibration is necessary if interlaboratory comparison of instrument performance and antibody binding is to be achieved. This report describes a new methodology to obtain a standard calibration plot that can be derived from all instruments and from which specific instrument‐independent performance parameters may be calculated that can be used to directly compare the performance and setup of these instruments. The requirements that the calibrated standards must meet are discussed, as well as the acceptable ranges proposed for the instrument‐independent performance parameters. In addition, data are presented from standard calibration plots generated by different flow cytometers in numerous laboratories. The corresponding Primary Performance Parameters calculated from these plots are presented and compared. It is expected that the use of this calibration method may help standardize flow cytometric measurements and will provide instrument‐independent performance parameters to monitor quality control of instruments and reagents. © 1996 Wiley‐Liss, Inc.

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