Soliman M, Kaplan E, Abdel-Latif A, Scherberg N, DeGroot L J
Department of Medicine, University of Chicago, Illinois 60637, USA.
J Clin Endocrinol Metab. 1995 Aug;80(8):2312-21. doi: 10.1210/jcem.80.8.7543112.
The effect of treatment on thyroid antibody production and T cell reactivity to thyroid antigens was studied in 15 patients with Graves' disease (GD) before and after thyroidectomy, 19 patients with GD before and after radioactive iodine (RAI) therapy, and 9 patients maintained euthyroid on antithyroid drugs (ATD). Twenty subjects matched for age and sex without known thyroid disease served as controls. In GD patients, the responses of peripheral blood mononuclear cells (PBMC) and TSH receptor (TSHR)-specific T cell lines to recombinant human TSHR extracellular domain, thyroglobulin, and TSHR peptides were examined on the day of surgery or RAI therapy (day 0) and also 6-8 weeks and 3-6 months thereafter. Reactivity to TSHR peptides before surgery was heterogeneous and spanned the entire extracellular domain. Six to 8 weeks after subtotal thyroidectomy, the number of patients' PBMC responding to any peptide and the average number of recognized peptides decreased. A further decrease in the T cell reactivity to TSHR peptides was observed 3-6 months after surgery. The responses of PBMC from Graves' patients before RAI therapy were less than those in the presurgical group. Six to 8 weeks after RAI therapy, the number of patients responding to any peptide and the average number of recognized peptides increased. Three to 6 months after RAI, T cell responses to TSHR peptides were less than those 6-8 weeks after RAI therapy, but still higher than the values on day 0. Responses of PBMC from patients with GD, maintained euthyroid on ATD, were lower than those before surgery or RAI therapy. The reactivity of T cell lines in different groups reflected a pattern similar to PBMC after treatment. TSHR antibody and microsomal antibody levels decreased after surgery, but increased after RAI therapy. The difference in the number of recognized peptides by patients' PBMC before RAI and surgery may reflect the effect of long term therapy with ATD in the patients before RAI vs. the shorter period in patients before surgery. The decreased T cell reactivity to thyroid antigens after thyroidectomy could be the result of removal of a major part of the thyroid gland or redistribution of suppressor-inducer T cells. The increased T cell response after RAI therapy is probably epitope specific, rather than a response to the whole TSHR molecule. Synchronous recognition of peptides 158-176 and 248-263 is important for the development of GD, and the loss of recognition of one of these epitopes may be an early sign of immune remission and a predictor of euthyroidism.
在15例格雷夫斯病（GD）患者甲状腺切除术前和术后、19例GD患者放射性碘（RAI）治疗前后以及9例服用抗甲状腺药物（ATD）维持甲状腺功能正常的患者中，研究了治疗对甲状腺抗体产生以及T细胞对甲状腺抗原反应性的影响。20名年龄和性别匹配且无已知甲状腺疾病的受试者作为对照。在GD患者中，于手术或RAI治疗当天（第0天）以及此后6 - 8周和3 - 6个月，检测外周血单个核细胞（PBMC）和促甲状腺激素受体（TSHR）特异性T细胞系对重组人TSHR胞外域、甲状腺球蛋白和TSHR肽段的反应。手术前对TSHR肽段的反应具有异质性，涵盖整个胞外域。甲状腺次全切除术后6 - 8周，对任何肽段有反应的患者PBMC数量以及识别肽段的平均数量均减少。术后3 - 6个月观察到T细胞对TSHR肽段的反应性进一步降低。RAI治疗前GD患者的PBMC反应低于手术前组。RAI治疗后6 - 8周，对任何肽段有反应的患者数量以及识别肽段的平均数量增加。RAI治疗后3 - 6个月，T细胞对TSHR肽段的反应低于RAI治疗后6 - 8周，但仍高于第0天的值。服用ATD维持甲状腺功能正常的GD患者的PBMC反应低于手术或RAI治疗前。不同组中T细胞系的反应性在治疗后反映出与PBMC相似的模式。TSHR抗体和微粒体抗体水平在手术后降低，但在RAI治疗后升高。RAI治疗和手术前患者PBMC识别肽段数量的差异可能反映了RAI治疗前患者长期服用ATD的效果与手术前患者较短治疗期的差异。甲状腺切除术后T细胞对甲状腺抗原反应性降低可能是甲状腺大部分切除或抑制诱导性T细胞重新分布的结果。RAI治疗后T细胞反应增加可能是表位特异性的，而非对整个TSHR分子的反应。对肽段158 - 176和248 - 263的同步识别对GD的发展很重要，失去对这些表位之一的识别可能是免疫缓解的早期迹象以及甲状腺功能正常的预测指标。
