Heterogeneity of TSH Receptor-directed Antibodies (TRAb) and Their Significance
In reviewing TRAb in Graves’ disease there is no longer need for debate about the role of TSAb itself. This antibody is generally accepted as causing hyperthyroidism through binding to a component of the TSH receptor and stimulation of adenylate cyclase. Formerly we used an assay based upon measurement of an increase in cAMP in human thyroid slices and found TSAb in over 90% of 102 patients (1). Now the procedure developed by Kasagi et al (2) and refined by Rapoport and his colleagues (3) has replaced the slice assay. This technique entails incubation of human thyroid cells in primary monolayer culture with patients’ IgG in hypotonic medium and subsequent measurement of cAMP that has been released into the medium. With this assay we find 100% positive results with IgG from Graves’ disease patients. This high sensitivity apparently is not associated with decreased specificity as judged by negative results with IgG from over 90 patients with thyroid disorders of nonautoimmune origin. A current alternate and more convenient procedure is the similar use of functioning rat thyroid (FRTL-5) cells in continuous culture (4), but not all IgG positive in the human thyroid cell assay give- a response in this system.
KeywordsIodide Acetylcholine Thymidine Hypothyroidism Hyperthyroidism
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