人甲状腺细胞的培养和功能研究及其应用

本文探讨获得正常和甲亢甲状腺细胞的方法及其培养条件，研究其对ＴＳＨ和甲状腺刺激抗体（ＴＳＡｂ）的反应性，分析两种甲状腺细胞在甲状腺特异性抗体测定中的临床价值。结果表明：１．正常和甲亢两种甲状腺组织经胰酶和胶原酶消化６０～９０分钟，即可获得大量活力良好的人甲状腺细胞；２．甲状腺细胞在以Ｅａｇｌｅ营养液为基础的培养条件下，随每孔细胞数的增多，对ＴＳＨ和ＴＳＡｂ刺激生成ｃＡＭＰ的量亦增加，并且在０～９６小时的培养时间里，甲状腺细胞ｃＡＭＰ的释放值递增；３．以正常或甲亢甲状腺细胞作为靶细胞，来检测病人血清ＴＳＡｂ和甲状腺刺激阻断抗体（ＴＳＢＡｂ），均具有较好的灵敏度和特异性。     

Graves病患者治疗前、后血清甲状腺刺激抗体和TSH结合抑制免疫球蛋白活性的观察

本文研究了Ｇｒａｖｅｓ病（ＧＤ）患者在抗甲状腺药物（ＡＴＤ）治疗前、后血清甲状腺刺激抗体（ＴＳＡｂ）和ＴＳＨ结合抑制免疫球蛋白（ＴＢＩＩ）的变化，发现治疗前ＴＳＡｂ和ＴＢＩＩ的检出率分别为９１．７％和７９．２％，治疗后两抗体的活性及阳性率均显著下降，表明抗甲状腺药可改善ＧＤ患者的免疫异常。ＴＳＡｂ和ＴＢＩＩ活性不相关，提示ＴＳＨ受体抗体（ＴＲＡｂ）具有异质性。ＴＳＡｂ和ＴＢＩＩ活性与血清甲状腺激素水平无相关关系，说明体外测定的ＴＳＡｂ或／和ＴＢＩＩ活性并不能完全反映甲亢的严重程度。     

Graves病患者甲状腺和外周静脉血中甲状腺特异性抗体的对比研究

本文对比研究１１例Ｇｒａｖｅｓ病（ＧＤ）和９例非ＧＤ患者甲状腺静脉血（ＴＶＢ）和外周静脉血（ＰＶＢ）中甲状腺刺激抗体（ＴＳＡｂ）、甲状腺球蛋白抗体（ＴＧＡｂ）和甲状腺过氧化物酶抗体（ＴＰＯＡｂ）的活性和Ｔ３、Ｔ４浓度。结果显示：（１）抗体阳性的ＧＤ患者，其ＴＶＢ中ＴＳＡｂ、ＴＧＡｂ和ＴＰＯＡｂ水平均显著高于ＰＶＥ的，ＰＶＢ和ＴＶＢ的ＴＳＡｂ活性呈显著正相关，这提示甲状腺本身是甲状腺特异性抗体产生的主要部位；（２）ＧＤ组和非ＧＤ组ＴＶＢ和ＰＶＢ的血清Ｔ３、Ｔ４不形成浓度梯度；（３）ＴＳＡｂ、ＴＧＡｂ和ＴＰＯＡｂ活性及其在ＴＶＢ和ＰＶＢ之间的活性梯度，与ＴＶＢ和ＰＶＢ中Ｔ３、Ｔ４浓度均无相关关系。     

血清抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体检测在甲状腺疾病诊断及甲亢预后判断中的价值

采用放免法检测甲状豚疾病患者抗甲状腺球蛋白抗体（ＴＧＡｂ）和抗甲状腺过氧化物酶抗体（ＴＰＯＡｂ）、并对部分Ｇｒａｖｅｓ病患者停药后随诊一年的结果进行分析。结果显示：（１）自身免疫性甲状腺疾病患者ＴＧＡｂ和ＴＰＯＡｂ活性及阳性率明显高于非ＡＩＴＤ，尤以桥本甲状腺炎为然。（２）ＧＤ治疗前及停药时ＴＧＡｂ和ＴＰＯＡｂ均阴性者与均阳性者停药一年内的复发率分别为０．５８３和０．２３１。（３）ＴＧＡｂ和ＴＰＯＡｂ均阴性，而停药时甲状腺刺激抗体（ＴＳＡｂ）阳性者，停药时ＧＤ复发的机率最大（０．９０９），提示ＴＧＡｂ和ＴＰＯＡｂ检测在ＡＩＴＤ诊断，鉴别诊断以及ＧＤ预后判断中具有重要的临床意义。     

Graves病手术前后血清甲状腺刺激免疫球蛋白的检测

本文用细胞化学法进行甲状腺刺激免疫球蛋白（ＴＳＩ）的测定。将４３例受试者分为正常对照组（１５例）和甲亢组（２８例），甲亢组中的１５例于手术前后分别测定ＴＳＩ，阳性率：正常组２０％；甲亢组５３．６％；１５例手术病人术前５３．３％、术后６．７％。作者认为：ＧＤ患者体内存在ＴＳＩ，支持ＴＳＩ是ＧＤ甲亢发病的主要因素的主张。大多数经过内科治疗甲亢症状未控制的ＧＤ患者，血清ＴＳＩ可被检出，经过手术治疗的ＧＤ     

Graves病患者治疗前,后血清甲状腺激素抗体和TSH结合抑制免疫？…

本文研究了Ｇｒａｖｅｓ病（ＧＤ）患者在抗甲状腺药物（ＡＴＤ）治疗前、后血清甲状腺刺激抗体（ＴＳＡｂ）和ＴＳＨ结合抑制免疫球蛋白（ＴＢＩＩ）的变化，发现治疗前ＴＳＡｂ和ＴＢＩＩ的检出率分别为９１．７％和７９．２％，治疗后两抗体的活性及阳笥率均显著下降，表明抗甲状腺药可改善ＧＤ患者的免疫异常。ＴＳＡｂ和ＴＢＩＩ活性不相关，提示ＴＳＨ受体抗体（ＴＲＡｂ）具有异质性。ＴＳＡｂ和ＴＢＩＩ活性与血清甲状腺激素     

联合应用抗甲状腺药物和甲状腺激素治疗Graves病的效果评价

本文研究抗甲状腺药物（ＡＴＤ）单独或与甲状腺激素联合应用，对Ｇｒａｖｅｓ病（ＧＤ）病情演变和转归的作用。联合用药组血清甲状腺刺激抗体（ＴＳＡｂ）下降的幅度明显大于单独应用ＡＴＤ组，其血清ＴＳＨ水平、药物性甲减的发病率以及停药后甲亢的复发率均显著低于单独用药组。提示ＡＴＤ与甲状腺制剂联合应用对ＧＤ具有更好的治疗效果。     

多抗F（ab＇）_2－ELISA测定人血清抗TG－Ab_2及意义

为了克服单抗测定甲状腺球蛋白独特型抗体（抗ＴＧ－Ａｂ＿２）的局限性，便于常规检测，我们建立了兔抗ＴＧ多克隆抗体的Ｆ（ａｂ＇）＿２－ＥＬＩＳＡ测定人血清中的抗ＴＧ－Ａｂ＿２．结果其抗ＴＧ－Ａｂ＿２阳性率：甲亢（Ｇｒａｖｅ＇３）为９．９％（７／７１），桥本氏甲状腺炎为４４．４％（４／９），甲状腺瘤为１６．７％（３／１８），ＳＬＥ为９．５％（４／４２），类风湿性关节炎为０％（０／３２），正常人为０％（０／３５）。     

多抗F（ab‘）2—ELISA测定人血清抗TG—Ab2及意义

为了克服单抗测定甲状腺球蛋白独特型抗体的局限性，便于常规检测，我们建立了兔抗ＴＧ多克隆抗体的Ｆ（ａｂ）２－ＥＬＩＳＡ测定人血清中的ＴＧ－Ａｂ２。结果其抗ＴＧ－Ａｂ２阳性率；甲亢为９．９％，桥本氏甲状腺炎为４４．４％，甲状腺瘤为１６．７％，ＳＬＥ为９．５％，类风湿性关节炎为０％，正常人为０％。     

灵敏的甲状腺微粒体抗体酶联免疫吸附分析的建立

甲状腺微粒体抗体（ＴＭＡｂ）或称甲状腺过氧化物酶抗体（ＴＰＯ－Ａｂ）已广泛用于人类甲状腺自身免疫性疾病的诊断，但粗提的人甲状腺微粒体制备物含有残留的甲状腺球蛋白（ＴＧ）和其它膜抗原，影响方法的灵敏度，我们采用亲和层析的方法，得到纯度较高的ＴＭ抗原，建立了灵敏的ＴＭＡｂ－ＥＬＩＳＡ。该方法的批内变异系数为３．２±０．０１％（ｎ＝８０），批间变异系数为８．３±０．０２％（ｎ＝８）；临床甲亢病人的阳性率为８０．０％（ｎ＝４６），与国内同类放免试剂盒相比，对Ｇｒａｖｅｓ病的阳性检出率提高２０％（ｎ＝２０），桥本氏甲状腺炎的阳性检出率提高１１．７％（ｎ＝２６）。     

Prognostic value of thyroid stimulating antibodies and TSH-binding inhibiting immunoglobulins in the follow-up of Graves' disease

Summary The prognostic value of the determinations of autoantibodies in Graves' disease is still questionable. So far, the role of different assay procedures used has not been intensively investigated. We simultaneously applied two different techniques, a radioreceptor assay and a T3 releasing in vitro assay, in the follow-up of patients with Graves' disease to directly compare the course of the antibody activities determined by these assays and to find out a prognostic significance of the composition of the antibody spectrum present. The initial activities of thyroid stimulating antibodies (TSAb) and TSH-binding inhibiting immunoglobulins (TBII) were not significantly correlated in patients before treatment. During a 12-month antithyroid medication antibody titres showed a concordant course in the majority of patients. In 6 of 25 patients, however, a discordant behaviour was clearly documented including dose-response curves. At the end of treatment, the patients could be divided into three groups: group I included 5 patients positive for both TSAb and TBII, group II 6 patients positive for TBII and negative for TSAb and group III 14 patients negative for both of them. During the following survey of 18 months all patients of group I, 2 patients of group II and 6 patients of group III experienced a relapse of hyperthyroidism. In conclusion, TSAb and TBII activities dissociate in some patients during antithyroid drug therapy. For the individual patient, the disappearance of both TSAb and TBII was no certain indicator for a longstanding remission of Graves' hyperthyroidism. The persistence of TSAb seems to be more reliably associated with persisting or rapidly relapsing disease than the persistence of TBII.Abbreviations cAMP Cyclic Adenosine Monophosphate - GD Graves' disease - T3 Triiodothyronine - T4 Tetraiodothyronine - TBII TSH-binding inhibiting immunoglobulins - TRH TSH releasing hormone - TSAb Thyroid stimulating antibodies - TSH Thyroid stimulating hormone     

Studies on thyroid cell surface antigens using cultured human thyroid cells.

Human thyroid cells in primary culture were used for studies of thyroid cell surface antibodies in patients with thyroid autoimmune disorders. Radioiodinated IgG preparations containing thyroid microsomal antibody (TMAb), thyroid stimulating antibody (TSAb) and/or thyroglobulin antibody (TgAb) were tested for binding to thyroid cells. Binding was observed with radioiodinated IgG from patients with Graves' disease, Hashimoto's thyroiditis and idiopathic myxoedema containing TMAb, irrespective of the presence of TSAb and TgAb, while negative results were obtained with normal IgG. A dose-dependent inhibition of binding to thyroid cells was produced by the addition of the corresponding unlabelled IgG preparations. Evidence for tissue specificity was provided by the absence of binding to human skin fibroblasts used as controls. Preabsorption with human thyroid microsomes completely abolished the binding to thyroid cells of a radioiodinated TMAb positive IgG preparation, while only incomplete removal of the reactivity to thyroid microsomes was produced by preabsorption with thyroid cells. These data suggest that some but not all microsomal antigenic determinants are expressed on the thyroid cell surface. Binding to thyroid cells was also observed with purified TgAb, indicating that thyroglobulin antigenic determinants are present on the surface of thyroid cells. No evidence of binding was obtained with a TSAb positive Graves' IgG preparation with undetectable TMAb and TgAb. Unlabelled IgG preparations containing TMAb from patients with either Hashimoto's thyroiditis or idiopathic myxoedema were shown to inhibit the binding to thyroid cells of radioiodinated TMAb positive Graves' IgG and vice versa. These data indicate that antibodies present in these thyroid autoimmune disorders share common thyroid cell surface antigens. However, the binding of radioiodinated IgG from a patient with idiopathic myxoedema was only partially inhibited by Graves' or Hashimoto's IgG, suggesting that some of the thyroid cell surface antibodies of idiopathic myxoedema may not be detectable in other thyroid autoimmune disorders.     

Long-Term Immunological Study in Graves’ Disease Treated with Thyroid Arterial Embolization

OBJECTIVE: The aim of this study was to investigate long-term immunological changes after the treatment of Graves' disease (GD) with thyroid arterial embolization and the effect of thyroid arterial embolization on the body's immunological functions. MATERIALS AND METHODS: Forty-one patients with clinically and laboratorily ascertained GD were treated with thyroid arterial embolization and followed up for 3-54 months following embolization. Prior to embolization and at 1, 3, 6, 12, and 36 months following embolization, thyroid autoimmune antibodies were tested respectively, including thyroid stimulating antibody (TSAb), thyrotropin antibody (TRAb), thyroglobulin antibody (TGAb), and thyroid microsomal antibody (TMAb), as well as subgroup lymphocytes of CD16+CD56+, CD19+, CD3+, CD3+CD4+ and CD3+CD8+. The autoimmune status of GD patients prior to embolization and the dynamic changes of the immunological function after embolization were analyzed. RESULTS: The therapy of thyroid arterial embolization could effectively decrease the activity/titer and positive rate of TRAb and the ratio of CD4+/ CD8+ to normal levels at 6 months following embolization, while the ratio of CD3+CD8+ increased gradually to normal level at 1 year following embolization. In patients with recurrence, TSAb and TRAb remained at a higher level, while the rate of CD3+CD8+ and the ratio of CD4+/CD8+ were not statistically significantly different from those before embolization. CONCLUSION: Immunological functional disorder exists in GD patients. The treatment method of thyroid arterial embolization can effectively resume the basic immunological function to normal range while patients with recurrence have no significant improvement, suggesting that thyroid arterial embolization has an effective role in adjusting the immunological function.     

自身免疫甲状腺病患者血清中IL-12和IL-18水平的分析

目的:提供自身免疫甲状腺病(AITD)患者体内Th1/Th2平衡紊乱的依据。方法:应用酶联免疫吸附法(ELISA)测定27例Graves病(GD)、24例甲状腺功能正常的桥本甲状腺炎(HT)、25例甲状腺功能低下的HT患者及20例正常对照者血清中IL12和IL18的浓度,并检测GD患者的甲状腺刺激性抗体。结果:GD患者与甲状腺功能正常的HT患者血中IL12、IL18水平无明显差异,但均高于正常对照者的相应水平。甲状腺功能低下的HT患者血中IL12和IL18的水平与正常对照者无差异。在GD和甲功正常的HT,IL18与IL12呈明显正相关。在GD,IL12和IL18均与其甲状腺刺激性抗体(TSAb)活性呈正相关。在甲状腺功能正常的HT还存在IL12和IL18二者与甲状腺球蛋白抗体(TgAb)的显著性正相关。结论:提示Th1型细胞在GD和HT两种AITD的发病中均起重要作用。通过抑制Th2型免疫反应,促进向Th1型的转变来治疗GD时,有可能导致病情恶化。     

Immunological of the Thyrotropin Receptor

Antibodies to the thyrotropin receptor appear to he responsible for hyperthyroidism in Graves disease. The antibodies, described as thyroid-stimulating antibodies (TSAb) mimic the effects of thyrotropin (TSH) by binding to the TSH receptor and activating adenylate cyclase. TSAb consist of an electrophoretically heterogeneous population of IgG and the thyroid-stimulating site is formed by combination of heavy and light chains in the Fab part of the molecule. Binding studies indicate that the TSAb molecule interacts monovalently with membrane bound TSH receptors and that TSAb consists of an antibody population which shows a restricted heterogeneity with regard to TSH receptor affinity. Studies in patients with Graves disease and hyperthyroidism indicate that the levels of TSAb correlate well with thyroidal iodine uptake and the absence of pituitary control of thyroid function. However in some patients with ophthalmic Graves' disease or autoimmune thyroiditis there is evidence of serum antibodies which interact with the TSH receptor but are unable to stimulate thyroid function.     

Immunological of the Thyrotropin Receptor

Antibodies to the thyrotropin receptor appear to he responsible for hyperthyroidism in Graves disease. The antibodies, described as thyroid-stimulating antibodies (TSAb) mimic the effects of thyrotropin (TSH) by binding to the TSH receptor and activating adenylate cyclase. TSAb consist of an electrophoretically heterogeneous population of IgG and the thyroid-stimulating site is formed by combination of heavy and light chains in the Fab part of the molecule. Binding studies indicate that the TSAb molecule interacts monovalently with membrane bound TSH receptors and that TSAb consists of an antibody population which shows a restricted heterogeneity with regard to TSH receptor affinity. Studies in patients with Graves disease and hyperthyroidism indicate that the levels of TSAb correlate well with thyroidal iodine uptake and the absence of pituitary control of thyroid function. However in some patients with ophthalmic Graves' disease or autoimmune thyroiditis there is evidence of serum antibodies which interact with the TSH receptor but are unable to stimulate thyroid function.     

Immunology of the thyrotropin receptor.

Antibodies to the thyrotropin receptor appear to be responsible for hyperthyroidism in Graves' disease. The antibodies, described as thyroid-stimulating antibodies (TSAb) mimic the effects of thyrotropin (TSH) by binding to the TSH receptor and activating adenylate cyclase. TSAb consist of an electrophoretically heterogeneous population of IgG and the thyroid-stimulating site is formed by combination of heavy and light chains in the Fab part of the molecule. Binding studies indicate that the TSAb molecule interacts monovalently with membrane bound TSH receptors and that TSAb consists of an antibody population which shows a restricted heterogeneity with regard to TSH receptor affinity. Studies in patients with Graves' disease and hyperthyroidism indicate that the levels of TSAb correlate well with thyroidal iodine uptake and the absence of pituitary control of thyroid function. However in some patients with ophthalmic Graves' disease or autoimmune thyroiditis there is evidence of serum antibodies which interact with the TSH receptor but are unable to stimulate thyroid function.