Thyrotropin receptor non-mediated thyroid stimulating immunoglobulin in Graves' disease.
There exists a consensus that hyperthyroid Graves' disease is caused by thyrotropin receptor (TSH-R) autoantibodies. To test the possibility that the TSH-R is the sole antigen for thyroid stimulating antibodies (TSAb), we compared bioactivities of Graves' IgGs between non-thyroid mammalian cells transfected with human TSH-R cDNA and the reference thyroid bioassay. A Graves' IgG with TSH-binding inhibitor immunoglobulin (TBII) activity (89%) markedly stimulated cAMP formation in both CHO-K1 cells transfected with TSH-R cDNA (340 microU/ml of TSH equivalent) and rat thyroid cells, FRTL-5, (410 microU/ml of TSH equivalent). In contrast, a TBII negative (-1.5%) IgG from another patient with Graves' disease showed a strong thyroid stimulating activity (87 microU/ml of TSH equivalent) when FRTL-5 cells were used for the assay. But no stimulating activity was observed in this IgG when CHO-K1 cells transfected with TSH-R cDNA were used, suggesting a possible existence of TSH-R non-mediated thyroid stimulating immunoglobulin in some cases of Graves' disease.
Endo
T
T
Third Department of Internal Medicine, University of Yamanashi Medical School, Japan.
Haraguchi
K
K
Ohmori
M
M
Ikeda
M
M
Ohta
K
K
Onaya
T
T
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification*; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000235:genetics; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification*; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000276:immunology*; D013972:Thyrotropin / Q000494:pharmacology; D014162:Transfection
D001323:Autoantibodies; D007074:Immunoglobulin G; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D004247:DNA; D000242:Cyclic AMP