Wallaschofski H, Kaczmarek M, Miehle K, Hentschel B, Paschke R
Department for Internal Medicine III, University of Leipzig, Germany.
Thyroid. 2000 Oct;10(10):897-907. doi: 10.1089/thy.2000.10.897.
Thyrotropin (TSHR) receptor antibodies that bind to the TSHR without stimulating the TSHR have been identified with a direct binding assay. Moreover, TSHR antibodies that exhibit thyroid epithelial cell stimulation without inhibition of 125I-bovine thyrotropin (bTSH) binding and vice versa have been described. These data suggest that stimulation or blocking of the TSHR by stimulating (TSAB) or blocking (TSBAB) TSHR antibodies could be possible without detectable bTSH-displacement activity. However, to date, possible differences between TSAB or TSBAB activity and inhibition of 125I-bTSH binding have not been systematically investigated. Therefore we compared inhibition of 125I-bTSH binding and TSAB or TSBAB activity of sera from 113 patients with Graves' disease treated with antithyroid drugs. To exclude the different assay conditions of previous investigations as possible confounding factors, we determined TSAB or TSBAB and inhibition of 125I-bTSH binding (TBIIW) with the same Chinese hamster ovary (CHO) cells expressing the human TSHR. Furthermore inhibition of 125I-bTSH binding was also determined as thyrotropin-binding inhibitory immunoglobulin (TBII) with solubilized porcine thyroid membranes (TRAK, Brahms, Berlin Germany) and the highly sensitive recombinant human TSH receptor assay (hTRAK, Brahms, Berlin Germany). Only 78% (54/69) of TSAB-positive and 78% (21/27) of TSBAB-positive sera detected with JP26 cells exhibit inhibition of 125I-bTSH binding measured as TBII or TBIIW. Furthermore, 59% (10/17) of sera without TSAB and TSBAB activity revealed inhibition of 125I-bTSH binding measured as TBII or TBIIW. We found significant differences between TSHR bioactivities (TSAB or TSBAB) and inhibition of 125I-bTSH binding. Moreover, there was no agreement between the detectable TSHR bioactivities (TSAB or TSBAB) and their detectable inhibition of 125I-bTSH binding. Therefore, it is very likely that TSH displacement by TSHR antibodies and stimulation or blocking of the TSHR by TSHR antibodies are different functions that do not need to occur together.
通过直接结合试验已鉴定出能与促甲状腺激素受体（TSHR）结合但不刺激TSHR的促甲状腺激素（TSH）受体抗体。此外，还描述了一些TSHR抗体，它们能刺激甲状腺上皮细胞但不抑制125I-牛促甲状腺激素（bTSH）的结合，反之亦然。这些数据表明，通过刺激（TSAB）或阻断（TSBAB）TSHR抗体来刺激或阻断TSHR，可能不会出现可检测到的bTSH置换活性。然而，迄今为止，TSAB或TSBAB活性与抑制125I-bTSH结合之间可能存在的差异尚未得到系统研究。因此，我们比较了113例接受抗甲状腺药物治疗的格雷夫斯病患者血清中125I-bTSH结合的抑制情况以及TSAB或TSBAB活性。为了排除先前研究中不同的检测条件可能作为混杂因素，我们使用表达人TSHR的相同中国仓鼠卵巢（CHO）细胞来测定TSAB或TSBAB以及125I-bTSH结合的抑制情况（TBIIW）。此外，还使用溶解的猪甲状腺膜（TRAK，德国勃林格殷格翰公司，柏林）和高灵敏度重组人促甲状腺激素受体检测法（hTRAK，德国勃林格殷格翰公司，柏林）将125I-bTSH结合的抑制情况测定为促甲状腺激素结合抑制性免疫球蛋白（TBII）。用JP26细胞检测到的TSAB阳性血清中只有78%（54/69）和TSBAB阳性血清中78%（21/27）表现出以TBII或TBIIW衡量的125I-bTSH结合抑制。此外，17份无TSAB和TSBAB活性的血清中有59%（10/17）表现出以TBII或TBIIW衡量的125I-bTSH结合抑制。我们发现TSHR生物活性（TSAB或TSBAB）与抑制125I-bTSH结合之间存在显著差异。此外，可检测到的TSHR生物活性（TSAB或TSBAB）与其对125I-bTSH结合的可检测抑制之间没有一致性。因此，很可能TSHR抗体引起的TSH置换以及TSHR抗体对TSHR的刺激或阻断是不同的功能，不一定同时发生。
