Thyroid stimulating immunoglobulins, also known as TSIs, are autoantibodies that are produced by the immune system in the setting of Graves' disease. Antibodies are molecules produced by white blood cells called B cells. B cells are stimulated to produce antibodies through a series of interactions with other white blood cells called helper T cells. These interactions transform B cells into plasma cells that secrete large amounts of antibodies. Each plasma cell secretes a unique type of antibody that is configured to bind to a specific target located in an invading organism or abnormal cancer cell. When an antibody binds to its target, it triggers a number of different reactions that ultimately lead to the destruction of the invading organism or abnormal cancer cell. In the setting of different autoimmune disorders, B cells are stimulated to produce antibodies that bind to specific targets located in normal cells and structures in the body. These antibodies are called autoantibodies.
TSIs that are produced in the setting of Graves' disease are autoantibodies that are configured to bind to structures located on the surface of the follicular cells in the thyroid gland. These structures are called TSH receptors. In the normal state, TSH receptors serve as docking stations for TSH secreted by the pituitary gland. When TSH circulating in the bloodstream binds to TSH receptors, signals are generated that stimulate the follicular cells to take up iodine that is used to produce thyroid hormone. These signals also stimulate the secretion of thyroid hormone from the thyroid gland.
TSIs are somewhat unique in that they do not directly promote the destruction of any normal cells or structures in the thyroid gland. Instead they mimic the action of TSH itself, driving the TSH receptors to generate signals that stimulate the production and secretion of thyroid hormone. This process is not governed by the normal feedback mechanism that regulates the secretion of TSH from the pituitary gland. As such, TSIs that bind to TSH receptors may stimulate the production and secretion of excess amounts of thyroid hormone.
TSIs may also bind to other target components located in the tissues that surround the eyeballs and the tissues that lie directly beneath the surface of the skin. This may lead to the development of thyroid eye disease and pretibial myxedema associated with Graves' disease.