ZnT8-specific bioanalytical tools for probing autoimmune destruction of pancreatic beta-cells in type-1 diabetes

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Type-1 diabetes is a chronic autoimmune disease characterized by the autoimmune destruction of the insulin-producing beta-cells in pancreatic islets. Autoantigens exposed on the cell surface are the earliest targets in the autoimmune process and thus useful markers for disease initiation and progression. At present, none of the clinically used diagnostic autoantibodies can recognize autoantigens on the beta-cell surface.

Zinc Transport-8 (ZnT8) is a major islet-specific membrane protein with a dynamic subcellular distribution. ZnT8 on the cell surface is a major antigenic target of islet autoimmunity and also a cell-identity marker of pancreatic beta-cells. Hence, surface-directed ZnT8 autoantibodies could be used to develop bioanalytical tools to address unmet needs in diagnostics.

In this proposed work, we will develop a membrane-reconstituted ZnT8 biosensor to detect cell-surface ZnT8 autoantibodies in the peripheral blood and evaluate their diagnostic value in patients with type-1 diabetes; The proposed research will yield new bioanalytical technologies that can enable detecting cell-surface autoantibodies in the earliest phase of islet autoimmunity development. The applications of these technologies to clinical practice will help establish evidence-based medicine for type-1 diabetes.