Identification of type 1 diabetes-related proteins

Abstract

Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease, whereby the insulin-secreting beta-cells of the pancreas are targeted and destroyed by the patient's immune system. Although genetic susceptibility is required for the onset of this autoimmune disorder, environmental factors, including infectious agents and diet, also play an important but poorly understood role. Recently, WP5212 was identified as the first candidate diabetes-related wheat protein. To identify candidate molecular mimics of this wheat protein in target tissues, a novel approach was developed. Antibodies raised against two short peptides of this dietary antigen cross-react with self proteins: an exocrine pancreatic 33 kDa protein and a 28 kDa protein in the islets, spleen and mesenteric lymph nodes. In order to identify additional putative targets, a broad spectrum polyclonal serum was generated. In addition, a second antigenic wheat protein was identified by screening a wheat cDNA expression library with antibodies from a highly wheat-sensitive patient with both T1D and celiac disease. Further characterization of candidate molecular targets and antigenic wheat proteins may reveal novel pathways related to environmentally-induced T1D.