Gene Expression in Nonspecific Orbital Inflammatory Disease

项目摘要 一组眼眶炎症性疾病，包括甲状腺眼病(TED)、肉芽肿伴多血管炎 (GPA)、结节病和非特异性眼眶炎症(NSOI)是导致视力丧失的重要原因， 疼痛和复视。有组织病理学的临床数据足以对一些患者做出诊断，但 对其他人来说不是。基因表达谱已被证明在几种癌症和其他疾病的诊断中是有用的 炎症性疾病。有待检验的具体假设包括：(1)TED患者的组织 不像GPA、结节病或NSOI患者的组织那样显示出与免疫相关的活性， 即使TED样本来自肌肉或新发疾病患者；(2)特异性 影响泪腺的炎症性疾病有明显的分子特征；(3)基于 在有限数量的转录本上，表达在眼眶组织或外周血中的基因可以补充或取代 眼眶活检；(4)NSOI患者的一部分患者患有可与GPA区分的疾病， 结节病和TED的分子图谱。这项研究的结果正在改变人们对 这些疾病每一种的发病机制。在分类/诊断和理解方面的这种改进 发病机制有可能导致治疗和结果的改善。

Project Summary A group of orbital inflammatory diseases, including thyroid eye disease (TED), granulomatosis with polyangiitis (GPA), sarcoidosis, and nonspecific orbital inflammation (NSOI) constitutes an important cause of vision loss, pain, and diplopia. Clinical data with histopathology are sufficient to make a diagnosis for some patients but not for others. Gene expression profiling has proven useful in the diagnosis of several cancers and other inflammatory diseases. Specific hypotheses to be tested include that: (1) tissue from patients with TED does not display nearly as much immune related activity as tissue from patients with GPA, sarcoidosis, or NSOI, even if the TED samples are derived from muscle or from patients with new onset disease; (2) specific inflammatory diseases affecting the lacrimal gland have distinct molecular signatures; (3) an algorithm based on a limited number of transcripts expressed in orbital tissue or peripheral blood can supplement or replace orbital biopsies; (4) a subset of patients with NSOI has a disease that can be distinguished from GPA, sarcoidosis, and TED by molecular profiling. The results from this study are changing the understanding of the pathogenesis of each of these diseases. This improvement in classification/diagnosis and in understanding pathogenesis has the potential to lead to improvement in therapy and outcome.