Background & Purpose

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PURPOSE

JDRF is soliciting applications for optimizing and validating existing technologies for predictive screening for T1D risk and autoimmunity to be applied for wide-spread use in population-based screening efforts, including newborn or childhood based screening.

BACKGROUND

Prevention of T1D represents a “cure” for those at-risk of developing the disease, and, in fact, may represent the most cost-effective approach to a cure. In addition, prevention of T1D is becoming increasingly important with the rising incidence of the disease. Over the last three to four decades, the incidence of T1D has increased at an annual rate of 3-5%, including penetration in the low-moderate human leukocyte antigen (HLA) risk groups, suggesting an altered paradigm for T1D development. In some countries, the largest increase in incidence has occurred in children between 1-5 years of age.

Currently, HLA genotype is the major genetic risk factor for T1D and can be used as an initial screen for risk. To date, assays of islet autoantibodies (AAbs) are the most robust approach to detect additional risk in these individuals as well as to detect risk in relatives of individuals with T1D or in the general population. Indeed , the 10-year risk of progression to symptomatic T1D with multiple islet AAbs (insulin, GAD65, IA-2 and ZnT8) is 70%, and the lifetime risk approaches 100%. However, the current clinical research practices for AAb screening, including screening for genetic risk in neonates or screening for AAbs in first-degree or second-degree relatives who are known to have an increased risk, detect only 40% and 15% respectively, of individuals who will progress to T1D. Only a relatively small proportion of HLA at-risk children develop T1D. Therefore, new approaches are required to increase the sensitivity and specificity of screening above these thresholds. Existing AAb assays used to predict the risk of T1D are also both cost- and blood volume-prohibitive for universal childhood screening.

The development of improved islet AAb assays to enable T1D risk detection in the general population or increased capability to screen in enriched populations (HLA at-risk, relatives) would facilitate recruitment for clinical research focused on identifying environmental triggers and natural history of T1D, along with interventions to prevent T1D.