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1700632525 （蔡　真）

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1700632530 内科学新进展 [:1700627012]

1700632531 内科学新进展 第五章　内分泌疾病

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1700632533 内科学新进展 [:1700627013]

1700632534 第一节　Graves病及Graves眼病的若干进展

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1700632536 摘　要　Graves病（GD）是一种器官特异性自身免疫性疾病，由T淋巴细胞介导，以TSH受体抗体（TRAb）作为特征性的抗体。T淋巴细胞的激活需接受双重信号，除T细胞抗原受体与MHC抗原复合物结合外，还需协同刺激信号参与，其中主要为B7-CD28/CTLA-4。GD药物治疗后复发率较高，如何降低GD的复发率目前仍是GD治疗中的难题。Graves眼病（GO）的发病机理主要为自身免疫，TSH受体（TSH-R）是最重要的自身抗原。正确仔细地判断GO的活动度和严重度对治疗方案的选择非常重要，但目前尚没有十分有效的评判标准。2008年欧洲甲状腺眼病组织（EUGOGO）公布了最新GO诊治共识，认为大剂量静脉使用激素治疗活动性和严重的突眼比口服激素效果更佳；131I治疗后1～3d开始加服强的松治疗，可将同位素治疗后15％左右的突眼加重比例降至几乎为零。

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1700632538 Abstract　Graves’ disease is an organ-specific autoimmune thyroid disease mediated by T cells and characterized by the presence of anti-thyrotropin receptor antibody（TRAb). In addition to the recognition of antigen（the first immune cell signal), immune cells（both T and B）also depend on secondary signals to enter an active proliferative and secretory state. Important second signals for the T cells include the B7-CD28/CTLA-4 family of cell surface molecules found on antigen presenting cells. Because of the high recurrence rate in the treatment of Graves’ disease, it remains a problem to manage the disease effectively with drugs and avoid the recurrence. Graves’ Orbitopathy（GO）is also an autoimmune disorder and thyrotropin receptor（TSHR）is the most important autoantigen. Grading the activity and the severity of GO is fraught with difficulties; however, classifying patients into active/inactive GO categories is frequently possible and greatly facilitates decision-making. In 2008, the European Group on Graves’ Orbitopathy（EUGOGO）published the consensus statement on the management of GO. Patients with severe or active GO should be treated with intravenous glucocorticosteroids as the first-line treatment. Patients with active GO given radioiodine should be offered prophylactic steroid cover（commencing with 0.3-0.5mg of prednisone/kg/bw per day orally 1-3 days after radioiodine). The risk that about 15% patients may develop new eye disease or experience progressions of pre-existing GO is almost eliminated by giving a short course of oral glucocorticoids after radioiodine.

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1700632540 一、Graves病免疫异常的研究进展

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1700632542 （一）体液免疫

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1700632544 Graves病（GD）是一器官特异性自身免疫性疾病，存在有TSH受体抗体（TRAb)、甲状腺球蛋白抗体（TGAb)、甲状腺过氧化物酶抗体（TPOAb)、T3-Ab、T4-Ab、钾／碘同向转运体（symport）抗体、第二胶质成分（second colloid component）抗体、甲状腺生长刺激或抑制抗体等。其中以TRAb作为特征性的抗体，可作为GD的诊断、病情程度、预后的估计和停药的指标之一及治疗方式选择的参考。

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1700632546 （二）细胞免疫

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1700632548 GD是T淋巴细胞介导的自身免疫性疾病。Graves病时CD4+T细胞（辅助性T细胞）和CD8+T细胞（细胞毒性T细胞）增多（也有研究发现CD8+T细胞并无增加），而抑制性T细胞下降。通过T－细胞抗原受体（T Cell Receptor, TCR)，CD8+T细胞识别结合于MHCⅠ类分子的抗原（大部分体细胞表达此抗原），CD4+T细胞识别结合于MHCⅡ类分子（仅存在于抗原提呈细胞，APC）的抗原（如GD时的表达于甲状腺滤泡细胞表面的TSH-R），T淋巴细胞对加工的抗原（抗原蛋白质的一部分）作出反应而被激活，T淋巴细胞激活产生细胞因子（如IL-2），刺激T淋巴细胞增殖，B淋巴细胞成熟及抗体产生。

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