Studies on multiple thyroid cell membrane-directed antibodies in Graves' disease.
Studies on multiple thyroid cell membrane-directed antibodies in Graves' disease.
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格雷夫斯病中多种甲状腺细胞膜定向抗体的研究。
DOI：
10.1172/jci112183
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
McKenzie,JM
中科院分区：
文献类型：
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作者：
Zakarija,M;Garcia,A;McKenzie,JM
免疫球蛋白 G 是从一位生过 3 个迟发性甲状腺功能亢进孩子的妇女的血清中获得的；该临床事件是由于母体血清中促甲状腺抗体（TSAb）和 TSAb 抑制剂的共存所致。目前的研究探讨了可能存在额外的甲状腺膜定向抗体。人类甲状腺切片、单层培养细胞和功能性大鼠甲状腺细胞 (FRTL5)，并测量环 AMP 浓度，用于 TSAb 测定。 125I-促甲状腺素（TSH）与其受体结合的抑制测定使用人甲状腺和FRTL5细胞以及人甲状腺和豚鼠脂肪细胞膜作为受体。所有活性均与 IgG kappa 相关。测试了通过人甲状腺和豚鼠脂肪细胞制剂吸附和解吸获得的 IgG kappa 级分以及亲本 IgG 的 F(ab')2 和 Fab 片段。结果表明，IgG具有三种活性，即TSAb；一种 TSH 结合抑制剂，在所有测试的物种和制剂中均具有活性，并且与 Fab 和 F(ab')2 一样对颗粒和溶解的甲状腺膜均有效； [0102] TSH结合增强剂（例如，约等于结合增加220%)，其仅以颗粒形式对人甲状腺膜相对特异，不被脂肪吸附，并且以F(ab')2形式具有活性，但最低限度以Fab形式具有活性。这一概念的提出是，通过体外实验或新生儿体内代谢清除，总 IgG 的稀释决定了对甲状腺刺激或 TSH 结合的影响。这种多种抗体的发生率及其相互作用仍有待确定。
Immunoglobulin G was obtained from the serum of a woman who had given birth to three children with a delayed onset of hyperthyroidism; the clinical events were due to the coexistence of thyroid-stimulating antibody (TSAb) and an inhibitor of TSAb in the maternal serum. The current studies explore the possible existence of additional thyroid membrane-directed antibodies. Human thyroid slices, cells in monolayer culture, and functioning rat thyroid cells (FRTL5), with measurement of cyclic AMP concentration, were used for TSAb assays. Assays of the inhibition of binding of 125I-thyrotropin (TSH) to its receptor used human thyroid and FRTL5 cells, and human thyroid and guinea pig fat cell membranes as receptors. All activities were associated with IgG kappa. Fractions of IgG kappa obtained by adsorption to and the desorption from human thyroid and guinea pig fat cell preparations and F(ab')2 and Fab fragments of the parent IgG were tested. Results indicated that there were three activities in the IgG, namely, TSAb; an inhibitor of TSH-binding that was active in all species and preparations tested, and was effective as Fab and F(ab')2 on both particulate and solubilized thyroid membranes; and an enhancer of TSH-binding (e.g., approximately equal to 220% increase in binding) that was relatively specific for human thyroid membranes only in particulate form, was not adsorbed by fat, and was active as F(ab')2, but minimally as Fab. The concept is developed that dilution of the total IgG, experimentally in vitro or by metabolic clearance in vivo in neonates, determines the effect on either thyroid stimulation or TSH-binding. The incidence of such multiple antibodies and their interaction remains to be determined.