Graves病患者血清0：3型耶尔森菌抗体测定及临床意义

应用ＥＬＩＳＡ法测定１４１例Ｇｒａｖｅｓ病患者血清０：３型耶尔森菌（ＹＥ）抗体。同时检测８１例正常人、３６例桥本甲状腺炎、１６例单纯性甲状腺肿、１０例甲状腺腺瘤或腺癌和４例亚急性甲状腺炎。阳性率分别为：正常对照组１６．０％，Ｇｒａｖｅｓ病组５５．３％，桥本甲状腺炎组４１．７％，单纯性甲状腺肿组２５．６％，甲状腺腺瘤和腺癌组１０．０％，４例亚急性甲状腺炎均为阴性。初步观察到ＹＥ抗体与ＴＳＨ受体抗体（ＴＲＡｂ）之间存在相关性（Ｐ＜０．０１）。ＹＥ抗体的测定对于研究耶尔森菌感染在Ｇｒａｖｅｓ病发病机制中的作用、明确病因、协助诊断和指导治疗均有重要意义。     

Graves病血清可溶性白细胞介素-2受体(SIL-2R)的变化及与甲状腺自身抗体的关系

按临床表现、体征、ＦＴ３、ＦＴ４、ＴＳＨ测定及治疗情况将６３例Ｇｒａｖｅｓ病患者分为未治组与治疗缓解组。用ＥＬＩＳＡ法测定血清ＳＩＬ－２Ｒ。结果显示血清ＳＩＬ－２Ｒ未治组与治疗缓解组相比是显著增高的（Ｐ＜０．０１）,但治疗缓解组与正常对照组无差异。血清ＳＩＬ－２Ｒ在未治组与ＦＴ３水平及甲状腺刺激抗体（ＴＳＩ）、甲状腺蛋白抗体（ＴＧ－Ａｂ）滴度呈正相关（ｒ分别为０．６７８、０．５８０、０．７３０,Ｐ均＜０．０１）。提示：血清ＳＩＬ－２Ｒ水平可作为判断Ｇｒａｖｅｓ病活动及治疗效果的一种有价值的免疫学指标     

甲状腺素在Graves病治疗中降低复发作用的研究进展

Ｇｒａｖｅｓ病在抗甲状腺药物治疗后加用甲状腺素不仅减轻突眼和甲状腺肿大，而且有助于降低Ｇｒａｖｅｓ甲亢的复发。Ｌ－Ｔ４降低甲亢复发的原因被认为是减少了甲状腺刺激抗体（ＴｓＡｂ）的生成。其机制为外源性Ｔ４抑制ＴＳＨ分泌而使ＴｓＡｂ产生减少从而减轻免疫反应；另外，细胞因子参与了Ｇｒａｖｅｓ病的自身免疫发病机制和调节着甲状腺细胞与炎症细胞之间的相互反应，加用Ｔ４使ＨＬＡ－ＤＲ异常表达减弱并调节免疫反应；甲状腺素还可能直接作用于特异的Ｂ淋巴细胞而减少ＴｓＡｂ的产生，最终使Ｇｒａｖｅｓ病得以长期缓解。     

Graves病血清可溶性白细胞介素—2受体（SIL—2R）的变化及与甲状腺自身抗 …

按临床表现,体征,ＦＴ３、ＦＴ４、ＴＳＨ测定及治疗情况将６３例Ｇｒａｖｅｓ病患者分为未治组与治疗缓解组,用ＥＬＩＳＡ法测定血清ＳＩＬ－２Ｒ,结果显示血清ＳＩＬ－２Ｒ未治组与治疗缓解组相比是显著增高的（Ｐ〈０．０１）,但治疗缓解组与正常对照组无差异,血清ＳＩＬ－２Ｒ在未组与ＦＴ３水平及甲状腺刺激抗体（ＴＳＩ）、甲状腺蛋白抗体（ＴＧ－Ａｂ）滴度呈正相关（ｒ分别为０．６７８、０．５８０、０．７３０、Ｐ均     

抗眼肌膜抗体与Graves眼病的关系

目的　探讨抗眼肌膜抗体（ Ｅ Ｍ Ａｂ） 与 Ｇｒａｖｅｓ 眼病的关系及其临床意义。方法　应用间接酶联免疫吸附测定（ Ｅ Ｌ Ｉ Ｓ Ａ） 和 Ｗｅｓｔｅｒｎ 印迹方法检测 Ｅ Ｍ Ａｂ 。结果　 Ｇｒａｖｅｓ 眼病的恶性突眼组抗体均值和阳性率均明显高于良性突眼组，后者高于无突眼甲状腺功能亢进（ Ｇ Ｄ） 组及对照组， Ｅ Ｍ Ａｂ 值与眼球突出度呈正相关，而与 Ｆ Ｔ３ 、 Ｆ Ｔ４ 、 Ｓ Ｔ Ｓ Ｈ、 Ｔ Ｇ Ａ、 Ｍ Ｃ Ａ 及病程无关，眼征好转后， Ｅ Ｍ Ａｂ 值明显下降。恶性组中相对分子量为９５ Ｋ Ｄ、６４ Ｋ Ｄ、５５ Ｋ Ｄ 和２３ Ｋ Ｄ 蛋白反应带、良性组中６４ Ｋ Ｄ 蛋白反应带有一定特异性，无特异性蛋白带。结论　抗眼肌膜抗体与 Ｇｒａｖｅｓ 眼病密切相关，其高低可反映眼病的活动性，能鉴别突眼的性质及分度，预测可发展为 Ｇｒａｖｅｓ 眼病的易感性，并可评估疗效及预后。     

EFFECT OF PSYCHOEMOTIONAL STRESS ONGASTROINTESTINALMOTILITY．

ＥＦＦＥＣＴＯＦＰＳＹＣＨＯＥＭＯＴＩＯＮＡＬＳＴＲＥＳＳＯＮＧＡＳＴＲＯＩＮＴＥＳＴＩＮＡＬＭＯＴＩＬＩＴＹ．ＭｉｃｈｉｏＨｏｎｇｏ，ＳｈｉｎＦｕｋｕｄｏ，ＴａｉｓｕｋｅＮｏｍｕｒａ．ＤｅｐａｒｔｍｅｎｔｏｆＰｓｙｃｈｏｓｏｍａｔｉｃＭｅｄｉｃｉ...     

类风湿关节炎中转化生长因子β1和细胞间粘附分子的变化

目的：了解类风湿关节炎（ＲＡ）血清、滑液和滑膜组织中转化生长因β１（ＴＧＦβ１）、细胞间粘附分子１（ＩＣＡＭ１）及细胞间粘附分子３（ＩＣＡＭ３）的变化。方法：采用ＥＬＩＳＡ及ＡＢＣ免疫组化方法检测ＲＡ患者血清、滑液和滑膜中ＴＧＦβ１、ＩＣＡＭ１和ＩＣＡＭ３的浓度和阳性程度。结果：ＲＡ血清中ＴＧＦβ１含量较低，而ＩＣＡＭ１含量明显升高，ＩＣＡＭ３含量正常，滑液中ＩＣＡＭ３含量低于血清含量。ＲＡ血清中ＴＧＦβ１含量与ＩＣＡＭ１含量呈中度负相关，与ＩＣＡＭ３含量无显著相关。在ＲＡ滑膜中巨噬细胞、滑膜衬里细胞和成纤维细胞ＴＧＦβ１染色阳性，巨噬细胞、滑膜衬里细胞、成纤维细胞和血管内皮细胞ＩＣＡＭ１染色阳性。结论：ＴＧＦβ１和ＩＣＡＭ１参与了ＲＡ的发生和发展过程，在ＲＡ慢性炎症中，ＩＣＡＭ１对炎细胞转移并聚集于滑膜可能有重要作用，ＲＡ外周血ＴＧＦβ１浓度减低伴随ＩＣＡＭ１浓度的增加。     

老年甲亢患者甲状腺刺激抗体检测及临床应用

以血清ＩｇＧ刺激培养的甲状腺机能亢进症患者甲状腺细胞，通过测定ｃＡＭＰ的释放值确定甲状腺刺激抗体（ＴＳＡｂ）的活性。结果显示：①老年Ｃｒａｖｅｓ病（ＧＤ）未治组ＴＳＡｂ活性显著高于ＧＤ缓解组与缓解停药组，３组患者ＴＳＡｂ的阳性率分别为８８．９％、４７．８％和４５．５％，甲状腺腺瘤组和对照组ＴＳＡｂ均为阴性。②ＧＤ缓解停药时５例ＴＳＡｂ阳性者中４例（８０．０％）于１年内复发，而６例阴性者仅１例（１６．７％）复发。③ＴＳＡｂ活性与血清Ｔ３、Ｔ４浓度无明显相关关系。提示ＴＳＡｂ测定对老年ＧＤ的诊断、鉴别诊断、治疗和预后判断有重要的指导意义。     

甲状腺疾病患者血清TSAb和TBII的检测

采用细胞培养生物学方法和放射受体分析法检测甲状腺疾病患者血清甲状腺刺激抗体（ＴＳＡｂ）和促甲状腺激素结合抑制免疫球蛋白（ＴＢＩＩ）。发现Ｇｒａｖｅｓ病未治组ＴＳＡｂ和ＴＢＩＩ活性与阳性率明显高于Ｇｒａｖｅｓ病缓解组和桥本甲状腺炎（ＨＴ）组，后两组ＴｓＡｂ和ＴＢＩＩ活性与阳性率高于甲状腺腺瘤组和正常对照组。Ｇｒａｖｅｓ病未治组、缓解组和ＨＴ组其ＴＳＡｂ和ＴＢＩＩ的检出率分别为９１．７％和７９．２％、４８．０％和４４．０％及２３．１％和６１．５％。甲状腺腺瘤组和对照组ＴＳＡｂ和ＴＢＩＩ均为阴性，其活性亦无统计学差异。血清ＴＳＡｂ与ＴＢＩＩ活性以及ＴＳＡｂ、ＴＢＩＩ活性与Ｔ＿３、Ｔ＿４、ＦＴ＿３和ＦＴ＿４浓度之间均无显著相关性。提示ＴＳＨ受体抗体具有异质性，联合检测这两种抗体对了解自身免疫性甲状腺疾病（ＡＩＴＤ）的发病机理，合理诊治甲状腺疾病具有重要的临床价值。     

细胞毒性T淋巴细胞相关抗原-4基因多态性与中国汉族人Graves''病的相关性研究

Ｇｒａｖｅｓ’病（ＧＤ）是一种自身免疫性疾病，细胞毒性Ｔ淋巴细胞相关抗原４（ｃｙｔｏｔｏｘｉｃＴｌｙｍｐｈｏｃｙｔｅａｓｓｏｃｉａｔｅｄａｎｔｉｇｅｎ４，ＣＴＬＡ４）是Ｔ细胞表面分子，其基因位于染色体２ｑ３３，ＣＴＬＡ４参与了免疫反应过程，我们以此作为候选基因，对ＣＴＬＡ４基因多态性与中国汉族人ＧＤ易感性的关联作了初步研究，现将结果报告如下。一、对象与方法１．对象：本院门诊及住院无亲缘关系的ＧＤ患者６２例，其中男性１４人，女性４８人，年龄（３６．１±１４．４）岁，按照甲亢症状、甲状腺…     

Relationship between thyroid autoimmunity and Yersinia enterocolitica antibodies.

It has previously been proposed that subclinical Yersinia enterocolitica infection may play a role in autoimmune thyroid disease (AITD). In this study, we investigated the relationship between the thyroid autoantibodies and the antibodies that produced against different serotypes of Y. enterocolitica. A total of 215 subjects were included into the study (65 newly diagnosed Graves' disease [GD], 57 Hashimoto's thyroiditis [HT], 53 nontoxic diffuse goiter [NTDG], and 40 subjects for control group [CG]). Thyroid receptor antibodies (TRAb), thyroid and agglutinating antibodies against Y. enterocolitica serotype O:3, O:5, O:8, O:9 were measured in the blood samples. The highest incidence of Y. enterocolitica antibody positivity was measured in GD (53.8% for O:3, 29.2% for O:5, 44.6% for O:8, and 40% for O:9) and followed by HT. In patients with GD, TRAb levels were also higher than in patients with HT, NTDG, and CG. There was no difference between NTDG and CG in respect to the titer levels and the positivity of both TRAb and Y. enterocolitica antibodies. There was also a weak linear correlation between TRAb level and the titer of antibodies against Y. enterocolitica antigens. It can be concluded that Y. enterocolitica infection may play a role in etiology of GD in Turkey.     

Immunoglobulins from Graves' patients stimulate phospholipase-A2 in FRTL5 thyroid cells.

The well documented ability of immunoglobulins G (IgGs) from Graves' patients to stimulate cAMP production is believed to be involved in the pathophysiology of this disease. It is still under discussion whether other intracellular messengers known to regulate thyroid function might play a similar role. This study shows that phospholipase-A2, a signal pathway unrelated to cAMP, is activated by Graves' IgGs. The IgGs from 67 patients with active Graves' disease, 8 patients with Graves' disease in remission, 5 patients with idiopathic myxedema, 2 patients with Hashimoto's thyroiditis, 57 patients with nonautoimmune thyroid disease, and 65 normal subjects were tested for their ability to stimulate phospholipase-A2 activity, as measured by arachidonic acid release from FRTL5 thyroid cells. The IgGs from patients with active Graves' disease caused a significant increase in arachidonic acid release compared to those from normal subjects, patients with nonautoimmune thyroid diseases, and patients with Graves' disease in remission (P less than 0.0001). The IgGs from active Graves' patients were also able to increase cAMP accumulation in FRTL5 cells. This effect did not correlate with the ability of the same IgGs to induce arachidonic acid release, suggesting that Graves' IgGs stimulate these two pathways by separate mechanisms. Moreover, a subgroup of IgGs that stimulated phospholipase-A2 did not increase the cAMP levels in FRTL5 cells. Our data suggest a novel mechanism of action of Graves' IgGs, the activation of phospholipase-A2, well distinguishable from the known effect on cAMP accumulation. The assay we describe could be helpful in improving the diagnosis and therapy of Graves' disease and in distinguishing it from nonautoimmune thyroid diseases. It also supplies the basis for a prospective subclassification of the Graves' patients, which might become useful to clarify the pathophysiology of this disease.     

Immunoreactivity to Yersinia enterocolitica antigens in patients with autoimmune thyroid disease.

Recent reports have suggested that Yersinia enterocolitica proteins encoded by a 72-kilobase virulence plasmid (known as release proteins and now identified as YOP2-5) are antigens recognized specifically by patients with Graves' disease and of potential etiological importance in this disorder. To examine this hypothesis, we evaluated immune responses to YOP in patients with autoimmune thyroid disease and in normal controls. Humoral responses to Yersinia were assessed using Western blots of crude Y. enterocolitica membrane proteins, Yersinia release proteins (YOP2-5), and human thyrocyte membranes. Twenty-four of 25 Graves' and 10 of 18 Hashimoto's patients showed reactivity with the release proteins, primarily the 67-, 46-, 36-, and 25-kilodalton bands. However, 17 of 24 normal subjects also demonstrated serological reactivity to the release proteins, and the pattern of reactivity of these sera was similar to that in the thyroid patients. No correlation was noted between serological reactivity to the release proteins and thyroid hormone levels. Patients and controls with serological reactivity to YOP also showed reactivity with Yersinia membranes. In addition to the serological studies, cellular immune responses were determined by peripheral blood mononuclear cell proliferation assays. Cellular reactivity to the release proteins was present in four of five Graves' and both Hashimoto's patients tested, but also in two of six nonthyroid illness patients with serological immunity to the release proteins. Intrathyroidal lymphocytes obtained from two Graves' patients demonstrated marked proliferation in response to the release proteins. These results indicate that there is no unique pattern of serological reactivity against Yersinia membranes or the release proteins in patients with autoimmune thyroid diseases and suggest that any causal relationship between Yersinia infection and Graves' disease may be related to T-cell immunity.     

EVALUATION OF TSH RECEPTOR ANTIBODY BY ''NATURAL IN VIVO HUMAN ASSAY'' IN NEONATES BORN TO MOTHERS WITH GRAVES'' DISEASE

Neonatal thyrotoxicosis induced by transferred TSH receptor antibody (TRAb) is the ideal human in-vivo experimental system for the evaluation of TRAb. The clinical significance of circulating TRAb in Graves' disease was evaluated by this 'natural in-vivo human assay'. TRAb activity in vitro was measured by radioreceptor assay (thyrotrophin-binding inhibitor immunoglobulin, TBII) and sensitive cAMP accumulation assay using FRTL-5 cells (thyroid-stimulating antibody, TSAb). Further, the binding-stimulation index (B-S index) was newly introduced, which was the most useful indicator for prediction of neonatal thyrotoxicosis, calculated as the product of TBII and TSAb (Tamaki et al., 1988a). Maternal serum TRAb indices showed highly significant correlations with the serum free T4 index (FT4I) and free T3 index (FT3I) in neonates (5-10 days after birth) born to 20 mothers with Graves' disease who had positive TBII and/or TSAb (FT4I: r = 0.825 for TBII, r = 0.908 for TSAb, r = 0.944 for the B-S index, P less than 0.001; FT3I: r = 0.622 for TBII, P less than 0.01, r = 0.812 for TSAb, r = 0.791 for the B-S index, P less than 0.001; n = 20). In contrast, in 57 untreated adult patients with hyperthyroid Graves' disease, the FT4I and FT3I levels were not correlated with any of the TRAb indices. The linear regression relationship between the B-S index and FT4I found in neonates was applied to values in adult patients with Graves' disease, and the patients were divided into three groups on the basis of the 95% confidence limit: high, normal, and low responders of thyroid hormone (FT4I) secretion to the B-S index. FT4I and the ratio of FT4I to the B-S index were highest and the TRAb indices were lowest in the high responders, while FT4I and the FT4I/B-S index ratio were lowest and the TRAb indices were highest in the low responders. The FT4I/B-S index ratio was inversely correlated with the titres of antithyroid microsomal antibody in all the adult patients with untreated Graves' disease (r = -0.288, P less than 0.05). The results suggest that in-vitro assays using animal thyroid cells and cAMP as an index of response are suitable for detecting circulating thyroid stimulating activity in vivo. Secretion of thyroid hormones in Graves' disease may be regulated not only by circulating thyroid-stimulating antibodies but also by intrathyroidal stimulatory factors or by inhibitory or destructive factors.     

Usefulness of the 2nd generation assay for anti-TSH receptor antibodies to differentiate relapse of Graves' thyrotoxicosis from development of painless thyroiditis after antithyroid drug treatment for Graves' disease

After antithyroid drug (ATD) treatment for Graves' disease, either a relapse of Graves' thyrotoxicosis or painless thyroiditis can develop. It is important to differentiate these two types of thyrotoxicosis because of the difference in required therapy. However, differentiation of thyrotoxicosis is usually difficult without radioactive iodine uptake (RAIU) which is not available in general practice. We investigated the clinical usefulness of the 2nd generation assay for anti-TSH receptor antibodies (TRAb) to differentiate these two types of thyrotoxicosis after ATD treatment for Graves' disease. We recruited 26 patients who developed thyrotoxicosis after ATD treatment for Graves' disease. These patients once became negative for TRAb and seemed to be in remission after ATD treatment. Upon development of thyrotoxicosis after ATD treatment, TSH, free T4, free T3 and TRAb were measured. TRAb were measured by the 2nd generation assay using recombinant human TSH receptors instead of porcine TSH receptors. Fourteen patients relapsed into Graves' thyrotoxicosis and 12 patients developed painless thyroiditis. Twelve (85.7%) of 14 patients with relapse of Graves' thyrotoxicosis were positive for TRAb. Eleven (91.7%) of 12 patients with development of painless thyroiditis after ATD treatment for Graves' disease were negative for TRAb. Levels of TRAb were significantly different between patients with relapse of Graves' thyrotoxicosis (4.86 +/- 6.45 IU/L) and those with painless thyroiditis (0.62 +/- 0.61 IU/L) (P<0.001). The 2nd generation assay for TRAb was useful to differentiate relapse of Graves' thyrotoxicosis from development of painless thyroiditis in patients who seemed to be in remission after ATD treatment for Graves' disease.     

鼠甲状腺细胞~(125)Ⅰ摄取法和cAMP释放法测定甲状腺刺激抗体的评价

本文分别仿Marcocci和Kasagi,用鼠甲状腺细胞株FRTL5 ~(125)I摄取法和cAMP释放法同时测定16例活动性GD患者的TSAb。所得TSAb阳性率,前法为56％,后法为94％,两者差异十分显著;TSAb指数,前法为1.19,后法为7.11,两者差异也十分显著。cAMP释放法应用于临床既方便又敏感:①细胞株可连续增殖,IgG的制备简易,培养基中的cAMP无需提取就直接用于测定;②比较GD患者未治35例和经治42例的测定结果,TSAb阳性率分别为91％和50％,两者差异十分显著;TSAb活性分别为1194％和276％,两者差异也十分显著。     

Graves' IgG stimulation of continuously cultured rat thyroid cells: a sensitive and potentially useful clinical assay

A continuously cultured line of normal rat thyroid (FRTL) cells can be stimulated by immunoglobulin preparations from patients with Graves' disease as measured by increases in intracellular cAMP levels. Responsiveness is concentration-dependent but is delayed in time relative to thyrotropin. Additionally, the cells respond to Graves' immunoglobulins which have no long-acting thyroid stimulator (LATS) activity and are negative when adenylate cyclase stimulation in human thyroid membrane preparations is assayed. No correlation exists between the stimulation activity and the ability of a Graves' immunoglobulin preparation to inhibit thyrotropin binding; cells are responsive even in the presence of such inhibitor activity.     

Continued suppression of serum TSH level may be attributed to TSH receptor antibody activity as well as the severity of thyrotoxicosis and the time to recovery of thyroid hormone in treated euthyroid Graves' patients.

The cause of continued suppression of serum thyroid-stimulating hormone (TSH) levels during antithyroid drug therapy in some Graves' patients is unclear. Recently, there has been a notable explanation involving the direct inhibition of TSH receptor antibody (TRAb) on TSH secretion in the pituitary gland. The purpose of this study is to verify the relation between TRAb or other clinical parameters and the continued suppression of serum TSH level during antithyroid drug therapy in patients with Graves' disease. We reviewed the medical records of patients with Graves' disease between 1995 and 2002 at Samsung Medical Center. We selected 167 Graves' patients who had been euthyroid for at least 12 months after recovery of serum T3 and T4 levels during the antithyroid drug therapy. We analyzed the correlation of the interval until recovery of serum TSH with the pretreatment clinical parameters. We compared the recovery rates of suppressed TSH levels between pretreatment thyrotrophin-binding inhibitory immunoglobulin (TBII)-positive (>15%) and TBII-negative patients. We also compared the clinical parameters between two groups at the time of diagnosis and after recovery of thyroid hormone. Pretreatment serum T3 level, (131)I uptake, TBII activity, and the time to recovery of T3 or T4/free T4 level showed significant positive correlations with the interval until recovery of serum TSH level ( p < 0.05). Recovery rates of serum TSH levels at 3 months after recovery of thyroid hormone were significantly lower in pretreatment TBII-positive patients than those in TBII-negative patients ( p < 0.01). Serum TSH levels were significantly lower in TBII-positive patients at 3 months after recovery of thyroid hormone ( p < 0.05). TBII activities inversely correlated only with serum TSH levels at 3months after recovery of thyroid hormone ( p < 0.001). In conclusion, continued suppression of serum TSH level may be attributed to TRAb activity as well as the pretreatment severity of thyrotoxicosis and the time to recovery of thyroid hormone in patients with Graves' disease during antithyroid drug therapy.     

A possible role of immunoglobulin E in patients with hyperthyroid Graves' disease.

To investigate the possible participation of immunoglobulin E (IgE) in the autoimmune process of Graves' disease, incidence of elevation of serum IgE level, TSH receptor antibody (TRAb), and thyroid status were studied in 66 patients with hyperthyroid Graves' disease, 54 patients with Hashimoto's thyroiditis, 19 patients with bronchial asthma, and 15 patients with pollen allergy. In hyperthyroid Graves' patients, elevation of serum IgE levels (> or = 170 U/mL) was found in 19 of 66 patients (29%), 11 of whom had hereditary and/or allergic conditions. Elevations of serum IgE levels were found in 63% of patients with bronchial asthma and in 40% of patients with pollen allergy. Mean values of serum IgE were the same in patients with hyperthyroid Graves' disease and with bronchial asthma. During methimazole treatment TRAb decreased without fluctuation of IgE levels in both groups. The decrease in TRAb was significantly greater in patients with normal IgE than in patients with IgE elevation. After prednisone administration, reduction in TRAb was greater in patients with normal IgE than that in patients with IgE elevation. High incidence of IgE elevation in hyperthyroid Graves' disease and slower reduction in TRAb in association with IgE elevation suggest a difference in the autoimmune processes in Graves' disease with and without elevation of IgE.