Funauchi M
Nihon Naibunpi Gakkai Zasshi. 1983 Dec 20;59(12):1912-27. doi: 10.1507/endocrine1927.59.12_1912.
It has recently been reported that many immunological abnormalities including the presence of TSH-receptor antibody (TRAb) were found in Graves' disease (GD). Circulating immune complexes (CIC) have also been detected in the serum of patients with GD as observed in systemic lupus erythematosus, which is thought to be a typical model of immune complex disease. The role of CIC in pathogenesis of hyperthyroidism, however, remains to be elucidated. Therefore, to clarify pathophysiological functions of CIC in GD, the levels of it in those patients were compared with their symptoms, those of TRAb, and lymphoblastogenesis (LBG) induced by phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). The subjects were forty patients with GD without any medication, one hundred and nine patients with GD on medication with methimazole (MMI), and fifteen healthy volunteers. CIC was measured by three different methods; polyethyleneglycol precipitation method (PEG), Clq binding assay (Clq), and Protein A binding assay (PA). The normal range was estimated with the mean plus or minus two times the standard deviation of normal controls. In untreated GD, CIC determined by PEG, Clq and PA widely distributed from normal range to high levels. The positive rates of CIC determined by PEG, Clq, PA, and any one method of these three were 17.5%, 22.5%, 30.0% and 52.5%, respectively. LBG using incorporation of tritiated thymidine showed the decreases in PHA and Con A, and the increases in PWM in patients with GD. The positive rates of CIC determined by PEG and PA were significantly higher in patients without goiter or with small one than those with large one (p less than 0.05). CIC measured by all three of PEG, Clq and PA showed negative correlation with TRAb significantly (p less than 0.05, p less than 0.01, p less than 0.01, respectively). On the other hand, CIC measured by Clq showed significant negative correlation with serum thyroxine concentration (p less than 0.01). The levels of CIC, TRAb and PWM-induced LBG decreased following the tapering dose of MMI sufficient to keep patients in euthyroid state. In consequence, there were no longer any correlations between CIC and TRAb after thyroid function was normalized. These observations suggest that CIC's which have huge molecular weight or have ability to bind Fc receptor on K cell, macrophage, neutrophil, and other immune cells may be one of the factors to inhibit the goitrogenic action of TRAb, and that CIC's which have ability to activate the complement system may be one of the factors to inhibit the stimulation of secretion of thyroid hormone by TRAb.(ABSTRACT TRUNCATED AT 400 WORDS)
最近有报道称，在格雷夫斯病（GD）中发现了许多免疫异常，包括促甲状腺激素受体抗体（TRAb）的存在。在GD患者的血清中也检测到了循环免疫复合物（CIC），这与系统性红斑狼疮中观察到的情况一样，而系统性红斑狼疮被认为是免疫复合物疾病的典型模型。然而，CIC在甲状腺功能亢进发病机制中的作用仍有待阐明。因此，为了阐明CIC在GD中的病理生理功能，将这些患者体内CIC的水平与其症状、TRAb水平以及由植物血凝素（PHA）、刀豆蛋白A（Con A）和商陆有丝分裂原（PWM）诱导的淋巴细胞生成（LBG）进行了比较。研究对象为40例未服用任何药物的GD患者、109例正在服用甲巯咪唑（MMI）的GD患者以及15名健康志愿者。通过三种不同方法测量CIC；聚乙二醇沉淀法（PEG）、Clq结合试验（Clq）和蛋白A结合试验（PA）。正常范围通过正常对照组平均值加减两倍标准差来估计。在未经治疗的GD中，通过PEG、Clq和PA测定的CIC广泛分布于正常范围至高值。通过PEG、Clq、PA以及这三种方法中的任何一种测定的CIC阳性率分别为17.5%、22.5%、30.0%和52.5%。使用氚标记胸腺嘧啶掺入法进行的LBG显示，GD患者中PHA和Con A诱导的LBG降低，PWM诱导的LBG升高。无甲状腺肿或甲状腺肿较小的患者中，通过PEG和PA测定的CIC阳性率显著高于甲状腺肿较大的患者（p<0.05）。通过PEG、Clq和PA这三种方法测量的CIC均与TRAb呈显著负相关（分别为p<0.05、p<0.01、p<0.01）。另一方面，通过Clq测量的CIC与血清甲状腺素浓度呈显著负相关（p<0.01）。随着MMI剂量逐渐减少至足以使患者保持甲状腺功能正常状态，CIC、TRAb和PWM诱导的LBG水平下降。结果，甲状腺功能正常后，CIC与TRAb之间不再存在任何相关性。这些观察结果表明，具有巨大分子量或具有与K细胞、巨噬细胞、中性粒细胞和其他免疫细胞上Fc受体结合能力的CIC可能是抑制TRAb致甲状腺肿作用的因素之一，而具有激活补体系统能力的CIC可能是抑制TRAb刺激甲状腺激素分泌的因素之一。（摘要截取自400字）
