Thyroglobulin release-stimulating activity in immunoglobulin G from patients with Graves' disease studied by human thyroid cells in vitro.
The ability of TSH or immunoglobulin G (G-IgG) from untreated patients with hyperthyroidism due to Graves' disease to stimulate thyroglobulin (Tg) release from human thyroid cells was studied. Thyroid tissue obtained from antithyroid drug-treated Graves' hyperthyroid patients was dispersed enzymatically and cultured in monolayers; medium was changed every 3 days. The cultured cells initially released large but declining amounts of Tg, independent of the presence of TSH (approximately 5 micrograms/dish on day 3 and approximately 1.5 micrograms/dish on day 6). After 6 days, TSH had a dose-dependent stimulatory effect on Tg release, and the peak response occurred on day 15. G-IgG-induced Tg release was found on the 12th day of culture and was maximal on day 18. Thyroid cells cultured for 12 days in the absence of TSH responded to TSH and G-IgG in a time- and dose-dependent fashion. Using 12-day cultures, Tg release-stimulating activity (Tg-RSA) was tested using 5 mg/ml (7.5 mg/dish) G-IgGs from 20 patients and 72-h incubation. The Tg-RSA of individual patients varied. However, significant correlations were found between Tg-RSA values and serum Tg concentrations or Tg-RSA and thyroid-stimulating immunoglobulin activities. No correlation was found between Tg-RSA and TSH binding inhibitor immunoglobulin activities. These results suggest that Tg-RSA can be an indicator of abnormal IgG of hyperthyroid Graves' patients. Whether the activity is identical with thyroid-stimulating activity remains to be clarified.
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism / Q000502:physiology*; D018828:Immunoglobulins, Thyroid-Stimulating; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D013997:Time Factors
D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D013972:Thyrotropin; D013954:Thyroglobulin