Featured Prize Lecture:

Pathophysiology and pathogenesis of Graves’ disease

Nagataki-Fuji Film Prize Lecture delivered during the International Thyroid Congress,
2010 September 16, Paris, France
Graves’ disease is an autoimmune disease characterized by hyperthyroidism, goiter and extrathyroidal manifestations, such as exophthalmos. Autoantibodies to the thyrotropin (TSH) receptor (TSHR) have been detected in patients with Graves’ disease and stimulating antibodies to TSHR are believed to induce hyperthyroidism. Therefore, TSHR and anti-TSHR antibodies (TSHRAb) play a key role in this disease. We performed molecular analyses of both TSHR (Akamizu et al. PNAS 1990) and TSHRAb (Akamizu et al. J Immunol 1996); the cloning of both TSHR and TSHRAb genes. These studies clarified the structure, function and interaction of TSHR and TSHRAb at the molecular level. Furthermore, using TSHRAb genes, we generated recombinant monoclonal TSHRAbs and a transgenic Graves’ model (Akamizu et al. Endocrinology 1999; Kim-Saijo et al. Eur J Immunol 2003). In addition, we studied genetic components in Graves’ disease, a disease in which multiple genetic and environmental factors are thought impair immunoregulation. We first demonstrated that a particular allele of the TSHR gene may contribute to GD susceptibility (Hiratani et al. JCEM 2005).