Rees Smith B, McLachlan S M, Furmaniak J
Endocrine Immunology Unit, University of Wales College of Medicine, Cardiff, United Kingdom.
Endocr Rev. 1988 Feb;9(1):106-21. doi: 10.1210/edrv-9-1-106.
This review considers recent developments in our understanding of the properties of TRAb, particularly measurement of the antibodies and their sites of action and synthesis. Two new assay methods have allowed considerable improvements in the sensitivity, specificity, precision, and ease of measuring TRAb. In particular: 1) receptor assays based on inhibition of receptor-purified labeled TSH binding to detergent-solubilized TSH receptors and 2) bioassays based on stimulation of cAMP release from monolayer cultures of isolated thyroid cells. Detailed studies with the two assays indicate that TSH receptor antibodies nearly always act as TSH agonists in patients with a history of Graves' hyperthyroidism. Studies in areas of dietary iodine sufficiency suggest that measurement of the antibodies at various stages in the course of treating Graves' disease can be of value in predicting the outcome of therapy. However, in areas of iodine deficiency, difficulties in the ability of patients' thyroid tissue to recover from the effects of antithyroid drugs may prevent the receptor antibodies from causing a relapse of thyrotoxicosis. Consequently, the predictive value of receptor antibody measurements would be expected to be lower in these geographical areas. Although patients with a history of Graves' hyperthyroidism nearly always have TRAb which act as TSH agonists, about 20% of patients with frank hypothyroidism due to autoimmune destruction of the thyroid have TRAb which act as TSH antagonists (blocking antibodies). There is some evidence that these blocking antibodies can cause hypothyroidism particularly in the neonate. With regard to the site of synthesis of TRAb, there is now direct evidence that they are synthesized by thyroid lymphocytes, particularly the lymphocytes in close proximity to thyroid follicular cells. This is consistent with the well established effects of antithyroid treatment (drugs, radioiodine, or surgery) on TRAb levels in addition to their effects on thyroid hormone synthesis. Recent studies using affinity labeling with 125I-labeled TSH have enabled elucidation of the structure of the TSH receptor. TSH receptors in human, porcine, and guinea pig thyroid tissue have a two-chain structure in which the TSH binding site is formed on the outside surface of the cell membrane by a water-soluble A subunit (Mr approximately 50 K). The A subunit is linked by a disulfide bridge and weak noncovalent bonds to the amphiphilic B subunit (Mr approximately 30 K). This subunit, which penetrates the lipid bilayer, probably forms the site for interaction of the receptor with the regulatory subunits of adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)
本综述探讨了我们对促甲状腺素受体抗体（TRAb）特性理解的最新进展，特别是抗体的检测方法及其作用和合成位点。两种新的检测方法在TRAb检测的灵敏度、特异性、精密度和便捷性方面有了显著提高。具体如下：1）基于抑制受体纯化的标记促甲状腺激素（TSH）与去污剂溶解的TSH受体结合的受体检测法；2）基于刺激分离的甲状腺细胞单层培养物中cAMP释放的生物检测法。对这两种检测方法的详细研究表明，在有格雷夫斯甲亢病史的患者中，TSH受体抗体几乎总是作为TSH激动剂起作用。在碘摄入充足地区的研究表明，在格雷夫斯病治疗的不同阶段检测抗体，对于预测治疗结果可能具有重要价值。然而，在碘缺乏地区，患者甲状腺组织从抗甲状腺药物作用中恢复的能力存在困难，这可能会阻止受体抗体导致甲状腺毒症复发。因此，预计在这些地区受体抗体检测的预测价值会较低。虽然有格雷夫斯甲亢病史的患者几乎总是有作为TSH激动剂的TRAb，但约20%因甲状腺自身免疫性破坏导致明显甲状腺功能减退的患者有作为TSH拮抗剂（阻断抗体）的TRAb。有一些证据表明，这些阻断抗体可导致甲状腺功能减退，尤其是在新生儿中。关于TRAb的合成位点，现在有直接证据表明它们是由甲状腺淋巴细胞合成的，特别是紧邻甲状腺滤泡细胞的淋巴细胞。这与抗甲状腺治疗（药物、放射性碘或手术）除了对甲状腺激素合成有影响外，对TRAb水平的既定影响是一致的。最近使用125I标记的TSH进行亲和标记的研究，已经能够阐明TSH受体的结构。人、猪和豚鼠甲状腺组织中的TSH受体具有双链结构，其中TSH结合位点在细胞膜外表面由水溶性A亚基（分子量约50K）形成。A亚基通过二硫键和弱非共价键与两亲性B亚基（分子量约30K）相连。这个穿透脂质双层的亚基，可能形成受体与腺苷酸环化酶调节亚基相互作用的位点。（摘要截选至400字）
