Differential splicing of the IA-2 mRNA in pancreas and lymphoid organs as a permissive genetic mechanism for autoimmunity against the IA-2 type 1 diabetes autoantigen

摘要

Type 1 diabetes results from the autoimmune destruc- tion of pancreatic β-cells in genetically susceptible individuals. Growing evidence suggests that genetically determined variation in the expression of self-antigens in thymus may affect the shaping for the T-cell repertoire and susceptibility to autoimmunity. For example, both allelic variation and parent-of-origin effects influence the thymic expression of insulin(a known type 1 diabe- tes autoantigen), and insulin gene transcription levels in thymus inversely correlate with susceptibility in both humans and transgenic models.