Study on the pathogenesis of thyroid-associated ophthalmopathy

甲状腺相关眼病（TAO）是一种自身免疫性疾病，与Graves病密切相关。然而，自身抗原的性质及其病理机制尚不清楚。在本研究中，我们试图（1）研究TAO患者的肥大眼肌组织和球后脂肪组织的细胞因子谱。(2)我们对33例TAO患者的14例眼肌组织和29例眶脂肪组织进行了研究。通过RT-PCR评估细胞因子基因表达。Th 1和促炎细胞因子主要在眼肌组织中检测到，而Th 2细胞因子主要在眼眶脂肪组织中检测到。通过CT评估的眼肌增大与眼肌中TNFα基因表达显著相关。另一方面，眼眶脂肪体积与IL-4和IL-10基因表达呈负相关。本研究对TAO患者的3例眼外肌组织和5例球后脂肪组织中的T细胞克隆性进行了研究。采用RT-PCR和SSCP方法检测T细胞受体Vβ基因的使用情况。在每个Vβ基因中检测到多条带，表明这些组织中存在T细胞克隆性。眼肌与眶脂肪组织之间在相同的活动度下有多条明显的带。本研究表明，与两个部位（眼肌组织和眶脂肪组织）之间的相同自身抗原反应的T细胞和与其他抗原反应的T细胞在TAO的这两个部位聚集。T细胞免疫可能在眼病的发展中起重要作用。

lt is generally accepted that thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder, which is closely associated with Graves' disease. However, the nature of autoantigen and its pathological mechanisms has not been clear. In the present study we have attempted (1) to investigate cytokine profile of the enlarged eye muscle tissues and retrobulbar fat tissues from patients with TAO. (2) We also investigated T cell receptor Vβ gene usage in these 2 sites of the lesions whether T cells recognize the same autoantigen or not.We have studied 14 eye muscle tissues and 29 orbital fat tissues from 33 patients with TAO. Cytokine gene expression was assessed by RT-PCR. Th1 and proinflammatory cytokines were predominantly detected in eye muscle tissues, while Th2 cytokines were predominantly detected in orbital fat tissues. Eye muscle enlargement, assessed by CT, was significantly correlated with TNFα gene expression in eye muscle. On the other hand, orbital fat volume was negatively correlated with IL-4 and IL-10 gene expression. These results suggest that both Th1 like and Th2 like immune reactions may play role in the development of two components of ophthalmopathy.We have investigated the T cell clonality in 3 extraocular muscle tissues and 5 retrobulbar fat tissues from patients with TAO. T cell receptor Vβ gene usage was assessed by RT-PCR and SSCP methods. Several bands were detected in each Vβ gene, suggesting the existence of T cell clonality in these tissues. Furthermore, there were several distinct bands at the same mobility between eye muscle and orbital fat tissues. The present study suggest that both T cells reactive with the same autoantigen between 2 sites (eye muscle tissue and orbital fat tissue) and T cells reactive with the other antigens, are accumulating in those 2 sites in TAO. T cell immunity may be important in the development of ophthalmopathy.