Final Report Summary - EURAPS (Autoimmune polyendocrine syndrome type I - a rare disorder of childhood as a model for autoimmunity)
The EURAPS project was created by bringing together leading scientists from Europe, Australia and China to work on the best available biological model for autoimmune disease, Autoimmune polyendocrine syndrome type I (APS-1), a rare hereditary disorder. At the time when the EURAPS consortium commenced, all groundbreaking research within this area had been conducted in Europe, but as this model gained in popularity, significant competition from United States (US) has evolved.
APS-1 is a rare hereditary disorder with autoimmune manifestations affecting both endocrine and non-endocrine tissues. The disease, also named autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED), has been instrumental in unravelling mechanisms critically involved in the induction of tolerance. APS-1 is caused by mutations in the autoimmune regulator (AIRE) gene, a putative transcription factor primarily expressed in medullary thymic epithelial cells where negative selection is thought to occur, to some extent also in rare peripheral lymphocytes. This rare monogenic disease shares many features with more common autoimmune disorders with complex patterns of inheritance, such as type 1 diabetes, Hashimoto's thyroiditis, autoimmune premature ovarian failure and Addison's disease.
During the course of this three years project, a series of important research problems have been attacked in collaboration between partners with complementary expertise through a set of five different scientific work packages resulting in many publications in top ranking journals such as New England Journal of Medicine, PLoS Medicine and Proceedings of National Academy of Sciences. As a result of the EURAPS project, a higher awareness among clinicians to diagnose more patients with APS-1 earlier has been created along with better and more uniform treatment modalities for APS-1 patients.
Importantly, as a model for autoimmune disorders, APS-1 will continue to provide a deeper insight into the mechanisms of tolerance induction and maintenance as well as autoimmunity in general. The identification of pathways important for the development of autoimmunity will undoubtedly identify novel drug targets that may be instrumental in the development of new treatment modalities.
APS-1 is a rare hereditary disorder with autoimmune manifestations affecting both endocrine and non-endocrine tissues. The disease, also named autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED), has been instrumental in unravelling mechanisms critically involved in the induction of tolerance. APS-1 is caused by mutations in the autoimmune regulator (AIRE) gene, a putative transcription factor primarily expressed in medullary thymic epithelial cells where negative selection is thought to occur, to some extent also in rare peripheral lymphocytes. This rare monogenic disease shares many features with more common autoimmune disorders with complex patterns of inheritance, such as type 1 diabetes, Hashimoto's thyroiditis, autoimmune premature ovarian failure and Addison's disease.
During the course of this three years project, a series of important research problems have been attacked in collaboration between partners with complementary expertise through a set of five different scientific work packages resulting in many publications in top ranking journals such as New England Journal of Medicine, PLoS Medicine and Proceedings of National Academy of Sciences. As a result of the EURAPS project, a higher awareness among clinicians to diagnose more patients with APS-1 earlier has been created along with better and more uniform treatment modalities for APS-1 patients.
Importantly, as a model for autoimmune disorders, APS-1 will continue to provide a deeper insight into the mechanisms of tolerance induction and maintenance as well as autoimmunity in general. The identification of pathways important for the development of autoimmunity will undoubtedly identify novel drug targets that may be instrumental in the development of new treatment modalities.