Subject(s)
Autoantibodies/blood , Graves Disease/physiopathology , Long-Acting Thyroid Stimulator/blood , Receptors, Thyrotropin/blood , Animals , Autoantibodies/chemistry , Autoantibodies/immunology , Calmodulin/metabolism , Cyclic AMP/biosynthesis , Graves Disease/blood , Graves Disease/immunology , Humans , Immunoglobulins, Thyroid-Stimulating , Long-Acting Thyroid Stimulator/immunology , Receptors, Thyrotropin/chemistry , Receptors, Thyrotropin/immunologyABSTRACT
Autoantibodies that occur in autoimmune thyroid disease and that interact with the TSH receptor are reviewed. Current limited understanding of the nature of the TSH receptor is detailed, and available assays for the different types of antibodies are described. The incidence, clinical significance, and interactions of the various antibodies are summarized.
Subject(s)
Autoantibodies/immunology , Receptors, Thyrotropin/immunology , Graves Disease/genetics , Graves Disease/immunology , Humans , Immunoglobulin G/immunology , Long-Acting Thyroid Stimulator/immunology , Thyroid Diseases/immunologyABSTRACT
The use of radioactive iodine (131I) in the treatment of Graves' disease results frequently in hypothyroidism requiring thyroid hormone supplementation. Relapse of Graves' disease months after inadequate treatment with 131I is well-recognized. However, late relapse of Graves' disease in a patient rendered hypothyroid by 131I years after therapy has not been reported. The authors discuss a patient who had a relapse of his Graves' disease 23 yr after treatment with 131I. Over the interval the patient had been on 1-thyroxine replacement for hypothyroidism and had persistently high levels of long acting thyroid stimulator or thyroid stimulating antibody. The authors speculate that the immune nature of Graves' disease may play a role in the observed clinical response to 131I.
Subject(s)
Graves Disease/therapy , Adult , Antibody Formation , Follow-Up Studies , Graves Disease/drug therapy , Graves Disease/radiotherapy , Humans , Hyperthyroidism/immunology , Hypothyroidism/chemically induced , Iodine Radioisotopes/therapeutic use , Long-Acting Thyroid Stimulator/immunology , Long-Acting Thyroid Stimulator/metabolism , Male , Thyroxine/administration & dosageSubject(s)
Hyperthyroidism/congenital , Antithyroid Agents/therapeutic use , Female , Fetal Diseases/drug therapy , Fetal Diseases/immunology , Graves Disease/immunology , Graves Disease/physiopathology , Humans , Hyperthyroidism/drug therapy , Hyperthyroidism/immunology , Hyperthyroidism/pathology , Immunity, Maternally-Acquired , Infant, Newborn , Long-Acting Thyroid Stimulator/immunology , Pregnancy , Pregnancy Complications/immunology , Pregnancy Complications/physiopathology , Thyroid Gland/embryologySubject(s)
Graves Disease/immunology , Immunoglobulin G/immunology , Adenylyl Cyclases/analysis , Animals , Biological Assay , Cell Membrane/enzymology , Cells, Cultured , Cyclic AMP/analysis , Densitometry/methods , Humans , Immunoglobulin G/analysis , Immunoglobulins, Thyroid-Stimulating , Iodides/metabolism , Long-Acting Thyroid Stimulator/immunology , Methods , Receptors, Cell Surface/metabolism , Receptors, Thyrotropin , Stimulation, Chemical , Thyroid Gland/analysis , Thyroid Gland/ultrastructure , Thyroid Hormones/metabolism , Thyrotropin/antagonists & inhibitors , Thyrotropin/metabolismSubject(s)
Autoantibodies/immunology , Immunoglobulin G/immunology , Long-Acting Thyroid Stimulator/immunology , Thyroid Gland/immunology , Animals , Autoimmune Diseases/etiology , Autoimmune Diseases/immunology , Guinea Pigs , Humans , Hyperthyroidism/etiology , Hyperthyroidism/immunology , Immunoglobulins, Thyroid-Stimulating , MiceABSTRACT
The authors describe 10 patients with associated diffuse toxic goiter and thrombocytopenic purpura and a female patient with associated goiter and a three-shoot autoimmune peripheral cytopenia. In 8 patients thyrotoxicosis preceded the appearance of thrombocytopenia, in 3 patients, both the conditions were diagnosed at a time. In 4 patients, the measurements were taken of the IgG content on the surface of platelets according to Dixon et al. In 3 patients, the IgG content turned out to be appreciably elevated, in one patient, the content of IgG was within normal, however the latter patient was examined after prednisolone intake that had given rise to an increase in the platelet count. Two patients who received radioactive iodine and three patients treated by thyrostatic drugs were later on subjected to splenectomy. In 4 patients, thrombocytopenic purpura remitted after subtotal strumectomy. One female patient was subjected to sectoral resection of the thyroid. Two years after surgery the patient, who was in an euthyroid state, developed thrombocytopenia which required splenectomy. It is possible that in the latter case there was no direct relation between the two diseases. The relationship between the two autoimmune diseases, diffuse toxic goiter and thrombocytopenic purpura, remained unclear in other 10 cases. The relationship between the diseases under consideration and approaches to specifying the character of such a relationship are under discussion.
Subject(s)
Autoimmune Diseases/etiology , Graves Disease/blood , Purpura, Thrombocytopenic/etiology , Adolescent , Adult , Autoantibodies/immunology , Blood Platelets/immunology , Female , Graves Disease/immunology , Humans , Long-Acting Thyroid Stimulator/immunology , Male , Middle Aged , Platelet Count , Thyroglobulin/immunologySubject(s)
Receptors, Immunologic/immunology , Antibodies/immunology , Antigen-Antibody Complex/immunology , Antigens/immunology , Antigens, Surface/immunology , Autoantibodies/immunology , Autoimmune Diseases/immunology , B-Lymphocytes/immunology , Graves Disease/immunology , Humans , Immunoglobulin Idiotypes/immunology , Immunoglobulins/immunology , Insulin Resistance , Long-Acting Thyroid Stimulator/immunology , Myasthenia Gravis/immunology , Receptor, Insulin/immunology , Receptors, Cholinergic/immunology , Receptors, Immunologic/genetics , Receptors, Interleukin-2 , T-Lymphocytes/immunologySubject(s)
Antibodies/immunology , Graves Disease/immunology , Immunoglobulins/analysis , Thyroid Gland/immunology , Animals , Female , Guinea Pigs , Humans , Immunoglobulin G/analysis , Immunoglobulin G/immunology , Immunoglobulins, Thyroid-Stimulating , Infant, Newborn , Long-Acting Thyroid Stimulator/analysis , Long-Acting Thyroid Stimulator/immunology , Receptors, Cell Surface/immunology , Thyrotropin/immunologyABSTRACT
TSH-receptor antibody (TRAb) activity and LATS activity of Graves' sera were compared. All of 50 LATS-positive cases were TRAb positive, although only 63% of LATS-negative cases were TRAb positive. Binding of 125I-TSH to the TSH receptors was inhibited dose-dependently by LATS-immunoglobulin. However, no correlation between TRAb activity and LATS activity was observed. TRAb was positive in 2 LATS-positive cases even when the symptoms of hyperthyroidism were controlled by treatment (antithyroid or radioisotope). The positive TRAb was not changed in 4 Graves' disease patients whose LATS activity had disappeared following antithyroid treatment. These clinical studies show that TRAb is more sensitive than LATS and suggest that LATS may be one of a heterogenous population of antibodies to the TSH receptor in Graves' disease.
Subject(s)
Autoantibodies , Graves Disease/immunology , Long-Acting Thyroid Stimulator/immunology , Receptors, Cell Surface/immunology , Graves Disease/therapy , Humans , Receptors, ThyrotropinABSTRACT
The question of whether autoimmune reactions result from abnormality of the autoantigen or of the autoantibody is fundamental. When reaction of the thyroid stimulating autoantibodies (TSaab) of Graves' disease with their autoantigen is measured in the mouse bioassay which has a very sensitive dose-response curve this provides a favourable system for detecting any influence of allotypic variation in the autoantigen on the affinity of the corresponding autoantibodies. Seven high potency long acting thyroid stimulator (LATS) sera were tested for degree of neutralization by soluble extracts from nine thyroids, using the mouse bioassay to measure changes in LATS activity. The thyroid extracts differed in neutralizing potency and the LATS sera differed in susceptibility to neutralization, but these variations were consistent enough to enable ranking and there were no significant exceptions from especially strong or weak reactions between any individual thyroid extract and any individual LATS serum. Even autologous reactants had no greater or lesser affinity than homologous ones. Five LATS protector (LATSP) sera, tested against six thyroid extracts, including their own, again showed no evidence of allotypic variation in the autoantigen, nor did 55 LATSP sera tested with one of four thyroid extracts. Altogether we have looked at over 200 individual reactions between soluble thyroid antigen and thyroid stimulating autoantibody (LATS and LATSP). We have not found a single significant instance of any exceptionally strong or weak affinities, even with autologous antigen. The findings are in accord with Burnet's theory that autoimmune reactions are due to the emergence of forbidden clones of lymphocytes, reactive with normal self antigens.
Subject(s)
Antibodies/analysis , Autoantibodies/analysis , Graves Disease/immunology , Long-Acting Thyroid Stimulator/immunology , Animals , Antibody Affinity , Antigen-Antibody Reactions , Autoantigens/immunology , Biological Assay , Cross Reactions , Dose-Response Relationship, Immunologic , Humans , Immunoglobulin Allotypes/immunology , Immunoglobulin G/immunology , Immunoglobulins, Thyroid-Stimulating , Mice , Thyroid Gland/immunologySubject(s)
Autoantibodies/immunology , Long-Acting Thyroid Stimulator/immunology , Receptors, Cell Surface/immunology , Antibodies/immunology , Autoimmune Diseases/immunology , Graves Disease/immunology , Humans , Immunoglobulin G/immunology , Immunoglobulins, Thyroid-Stimulating , Receptors, Thyrotropin , Thyroiditis, Autoimmune/immunologyABSTRACT
An extraordinary case: large cutaneous tumors, intense "endocrine" exophthalmos, macroglossia, acropachie, prétibial mucinosis, diffuse myxodermia, symptoms of systemic involvement.
Subject(s)
Graves Disease/complications , Myxedema/pathology , Autoimmune Diseases/immunology , Humans , Leg Dermatoses/etiology , Leg Dermatoses/immunology , Leg Dermatoses/pathology , Long-Acting Thyroid Stimulator/immunology , Male , Middle Aged , Myxedema/etiology , Myxedema/immunology , Postoperative Complications , Thyroiditis, Autoimmune/pathologySubject(s)
Graves Disease/immunology , Receptors, Cell Surface/immunology , Thyroid Gland/immunology , Animals , Antibody Affinity , Autoantibodies/biosynthesis , Graves Disease/etiology , Guinea Pigs , Humans , Hyperthyroidism/immunology , Immunoglobulin G/immunology , Long-Acting Thyroid Stimulator/immunology , Mice , Receptors, ThyrotropinSubject(s)
Goiter, Nodular/complications , Graves Disease/complications , Hyperthyroidism/etiology , Chorionic Gonadotropin/physiology , Female , Goiter, Nodular/pathology , Goiter, Nodular/physiopathology , Graves Disease/genetics , Graves Disease/immunology , Humans , Hyperthyroidism/chemically induced , Iodine/adverse effects , Long-Acting Thyroid Stimulator/immunology , Male , Neoplasms/complications , Pregnancy , Thyroid Neoplasms/complications , Thyroiditis/complications , Thyrotropin/physiologySubject(s)
Autoimmune Diseases/immunology , Thyroid Diseases/immunology , Animals , Autoimmune Diseases/etiology , Autoimmune Diseases/genetics , B-Lymphocytes/immunology , Cell Migration Inhibition , Graves Disease/immunology , Humans , Immunoglobulin G/immunology , Long-Acting Thyroid Stimulator/immunology , Major Histocompatibility Complex , Mice , Microsomes/immunology , Receptors, Cell Surface/immunology , Receptors, Thyrotropin , T-Lymphocytes/immunology , T-Lymphocytes, Regulatory/immunology , Thyroglobulin/immunology , Thyroid Diseases/etiology , Thyroid Diseases/genetics , Thyroid Gland/immunology , Thyroiditis, Autoimmune/immunologyABSTRACT
Graves' ophthalmopathy usually occurs in association with hyperthyroidism. Its occasional occurrence in the absence of thyroid disease suggests, however, that it may be a separate autoimmune disorder. While the evidence supporting an autoimmune pathogenesis is considerable for the ophthalmopathy, it is not so impressive as that for Graves' hyperthyroidism: orbital antibodies have not been convincingly demonstrated and autoantigens have not been identified. On the other hand, in patients with Graves' ophthalmopathy the orbital tissues and eye muscle membranes are infiltrated with lymphoid cells and show evidence of cell-mediated immune reactions. Although there is some evidence that binding of thyroid stimulating hormone fragments and thyroglobulin-antithyroglobulin immune complexes to eye muscle membranes may be important in the pathogenesis of the ophthalmopathy, this needs to be confirmed. The mechanism for the association of hyperthyroidism and ophthalmopathy is unknown, but the association likely reflects an influence of thyroid hormones on the immune system. In view of the autoimmune pathogenesis the logical treatment of Graves' ophthalmopathy appears to be immunosuppression.