Auto-immunity in Thyroid Disease

Immune Mechanisms In Graves' Disease

“…This review will emphasize that our present understanding of normal immune mechanisms of antibody formation, in addition to our comprehension of the perturbations leading to Graves' disease, is inadequate. Present concepts suggest that TSH receptor antibodies may be caused by an antigen specific suppressor cell defect, thus allowing unabated production of TSH receptor antibodies (4)(5)(6). It is our opinion, for which the accumulated evidence is presented in this review, that Graves' disease represents a tremendously complex series of immunologic interactions which result in the generation of stimulating TSH receptor antibodies.…”

“…Heterogeneity of TSH receptor antibodies would be expected to result in Graves' sera containing antithyroid antibodies of multiple IgG subclasses (4,130,132). In humans there are four IgG subclasses denoted IgGi_ 4 ; these subclasses differ slightly in their ability to participate in immune reactions.…”

“…Today it is widely believed that Graves' disease is an autoimmune disorder caused, at least in part, by circulating TSH receptor antibodies (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). These TSH receptor antibodies may be formed by a combination of factors including helper/suppressor cell perturbations, abnormalities in antigen-specific (TSH receptor) suppressor cells, or by alterations in the relationship of class II HLA antigens to antigen presenting cells, resulting, finally, in the production of TSH receptor antibodies.…”

“…At present, however, the overwhelming evidence is that patients with Graves' disease have TSH receptor antibodies which can interact with the TSH receptor to either block or stimulate cAMP and iodide uptake (1)(2)(3)(4)(5)(6)(7)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32).…”

“…G RAVES' DISEASE is an autoimmune disorder characterized by the presence of stimulatory anti-TSH receptor antibodies which are thought to act via the TSH receptor to increase iodide uptake and cyclic AMP (cAMP), in turn, resulting in T 3 and T 4 production and secretion (1)(2)(3)(4)(5)(6)(7). There have been many clinical articles published summarizing the clinical and laboratory manifestations of Graves' disease (1-7) and excellent reviews of "Autoimmune Thyroid Disease" by Weetman and McGregor (2) and of "Endocrine Ophthalmopathy" by Jacobson and Gorman (8) have been published recently.…”