Immune Disorders in Hashimoto's Thyroiditis: What Do We Know So Far?
Autoimmune thyroiditis (Hashimoto's disease) is a polygenic disorder with complex etiopathogenesis. Apoptosis is proposed as one of its mechanisms. Programmed cell death is essential for the maintenance of homeostasis, but when it is deregulated, it may contribute to the development of disorders. There are two apoptotic pathways: intrinsic and extrinsic. The extrinsic pathway maybe activated among others through FasL binding to its receptor Fas. The FasL induced apoptotic pathway proceeds with cascade activation of following caspases, with final effector proteins recruitment. There is also a group of inhibitory proteins of apoptosis, where the Bcl-2 protein predominates. In the course of Hashimoto's disease the following aberrations are encountered: increased Fas/FasL expression, caspases and Bid protein concentrations, decreased Bcl-2 concentration and at the same time increase of Bcl-2 within intrathyroidal lymphocytes. They favor the thyrocytes apoptosis and thyroid gland destruction. Synergistically acting proapoptotic cytokines IFN-gamma and TNF or IL-beta, are considered to be major factors of the abnormalities mentioned above. TSH, T3 and T4, TSAb and TSBAb antibodies and iodide concentration may also play a role in pro- and antiapoptotic factors expression regulation. The role of TRAIL protein in the course of Hashimoto's thyroiditis needs evaluation. The current data on the role of apoptosis in the etiopathogenesis of the autoimmune thyroiditis will be presented and discussed.