Auto-Immune Disease: Type I Diabetes

Investigators: Shane Miersch, Ph.D. Sahar Sibani, Ph.D.

Collaborators: Mark Atkinson, Clive Wasserfall and Des Schatz (University of Florida), Tanya Logvinenko (NEMC)

Type 1 diabetes stems from a defect in immune surveillance that compromises self-tolerance to pancreatic islet antigens and results in the selective targeting, destruction and progressive loss of beta cells. This ultimately impairs the ability to secrete insulin, maintain blood glucose homeostasis and if left untreated will result in mortality. This disease affects 10-20 million persons worldwide, altering the lifestyle of the afflicted and pre-disposing them to a host of severe secondary complications. Humoral autoantibodies to pancreatic antigens can be detected prior to presentation of overt symptoms and have both diagnostic and prognostic clinical value. Indeed, the recent discovery of novel autoantigens suggests that there exist additional blood-borne markers of Type 1 diabetes.

Thus this project seeks to identify novel autoantibodies by serological screening of diabetic sera against a 6000+ library of human antigens. Screens will be conducted using the recently developed, high density, in situ-expressed, protein microarray technology – termed NAPPA (Nucleic Acid Programmable Protein Array), developed within our lab.

By employing such a broad set of potential molecular targets our aims are 1) to identify, through multiple confirmatory rounds of screening, a panel of serum reactive antigens to which autoantibodies associated with disease can be detected and 2) to test the ability of identified serum-reactive antigens to accurately discriminate between those with autoimmune diabetes and those without. Successful achievement of these goals holds the promise of enhancing early detection of disease and broadening opportunities for intervention via antigen-specific immunotherapy.

Once complete, we further hope to understand the biological importance of newly identified targets through an exploration of the expression, localization and interactions of the antigen, as well as changes in antibody responses over time in hopes of illuminating the autogenetic origins of Type 1 diabetes.