Inhibitory Effect of Thyroid Blocking Antibody (TBAb) on the Thyroid Stimulatory Effect of Human Chorionic Gonadotropin (HCG ) and Equine Chorionic Gonadotropin (ECG)

Abstract

Two kinds of TSH receptor (R) antibody (TRAb) are known. One is the the thyroid stimulating antibody (TSAb) active in hyperthyroidism and other is the thyroid blocking antibody (TBAb) causing primary hypothyroidism. TBAb blocks the thyroid stimulating activity of TSH by the inhibition of TSH binding to the TSHR. TBAb also blocks the thyroid stimulating activity of TSAb by inhibition of TSAb binding to the TSHR [1,2].Human chorionic gonadotropin (HCG) has the thy- . Four thousand iu/mL of HCG and ECG preparation caused cAMP production similar to 100μU/mL of bovine (b) TSH. The inhibitory effect of TBAb on cAMP production by this amount of HCG or ECG was then examined. The inhibitory effect of TBAb on cAMP production by HCG and ECG was similar to bTSH, and TBAb positive sera with more than 40 iu/L TBii activity completely blocked cAMP production by HCG, ECG and bTSH. This suggests that common alpha -subunit of both HCG and TSH are involved in the inhibitory effect of TBAb. Previous reports demonstrated that the thyroid stimulating activity of thyroid stimulating antibody (TSAb) was blocked by deglycosyalted HCG (competitive antagonist of TSH binding to TSHR). The fact and our present study suggest that TSH, HCG ECG, TSAb and TBAb have a similar binding site (alpha-subunitmimicking binding site) on the TSH receptor.

Neutralization and purification of thyroid stimulating antibody (TSAb) and thyroid blocking antibody (TBAb) by heterophilic antibody to animal IgG in Graves' disease

“…Lately, it has been reported that thyroid stimulating type human monoclonal Ab (M22) has similar TSH receptor(R) binding site as TSH; TSHR binding site of H-chain and L-chain of Fab portion of M22 is similar as α-and β-subunit of TSH, respectively [32]. We also reported that TSAb and TBAb have the similar TSH R binding site as α-subunit of TSH [33]. These reports suggest that Fab portion of LATS (TSAb)-IgG is composed of mammalian TSH-like structure except human TSH.…”

Characterization of Apparently Paradoxical Thyrotropin Binding Inhibitory Immunoglobulins With Neutral Bioactivity

“…In fact, although some weak mAbs created in mice showed weak stimulatory activities to the TSH-R, the TBII activities were also weak [ 24 ]. The TBII activities of human chorionic gonadotropin were weak, as well [ 3 ].…”

“…7 ) for 1 or 2 hours after the reaction with rhTSH-R. After that, cAMP activities in serum samples S caught up to the level of the control. In contrast, potent blocking serum samples B [ 3 ], or serum samples No. 1 in Fig.…”

“…She became hyperthyroid recently and her TSAb activity rose (384%-1480%). The serum samples of patient B were kindly provided by Dr Ochi [ 3 ]. Institutional ethics committee approval for the study was obtained and, after obtaining written informed consent, serum samples at 752 time points from 2015 to 2021 were obtained from 442 GD patients in total, who were either untreated, treated with antithyroid drugs, or in remission, in addition to the previous report [ 2 ].…”