Immunogenetic mechanisms in Behcet's Disease

在美国，葡萄膜炎导致了大约3万例新的法定失明，占所有失明病例的2.8-10%(1)。Behets病(BD)是一种病因不明的慢性复发性多系统炎症性疾病，以眼内炎症、口腔和粘膜溃疡、皮肤损害和炎症为特征，可影响身体其他器官，如关节、肠道、附睾部、血管和中枢神经系统(2)。对于对全身免疫抑制治疗无效或不耐受的BD眼部表现的患者，是否需要一种更安全、更有效的治疗方法值得进一步研究。有报道明确了白介素17A在Behets病发病机制中的特殊作用。 该方案将评估免疫介体，包括细胞因子谱(可溶的和细胞内的)、淋巴细胞表型和调节性T细胞。表观遗传修饰也将被研究。 此外，有人提出，美国/西方的BD患者可能与他们的地中海患者具有不同的疾病特征。将对美国/西方和地中海BD患者的疾病特征进行比较和评估。已经参与其他NIH方案的BD参与者的血液样本将被收集(特别是来自NIH方案03-AR-0173的当前参与者，其中NEI是协作者)，其中参与者已经同意其他或未来使用样本。总而言之，结果将根据不同种族的疾病和疾病的临床特征(例如，眼部和非眼部受累、活动期和静止期疾病)进行分析。 匿名血液样本(种族、年龄和性别匹配)将从NIH临床中心(CC)血库获得，并将与疾病样本进行比较。

Uveitis is responsible for approximately 30,000 cases of new legal blindness in the United States and 2.8-10% of all cases of blindness (1). Behets disease (BD) is a chronic relapsing multisystem inflammatory disorder of unknown etiology that is characterized by intraocular inflammation, oral and mucosal ulcerations, cutaneous lesions and inflammation that may affect other body organs such as the joints, intestinal tract, epididymis, blood vessels and the central nervous system (2). The need for a safer and more effective therapy for patients with ocular manifestations of BD refractory to or intolerant of systemic immunosuppressive therapy warrants further investigation. Reports define a specific role for interleukin (IL)-17A in the pathogenesis of Behets disease. This protocol will evaluate immune mediators including cytokine profiles (soluble and intracellular), lymphocyte phenotyping and regulatory T-cells in participants with BD. Epigenetic modifications will also be studied. Additionally, it has been suggested that American/Western BD patients may have different disease characteristics than their Mediterranean counterparts. The disease characteristics of American/Western and Mediterranean BD patients will be compared and evaluated. Blood samples from BD participants that have participated in other NIH protocols where participants consented for other or future use of samples has been obtained will be collected (particularly from current participants of NIH protocol 03-AR-0173 in which NEI is a collaborator. In summary, the results will be analyzed with respect to disease in different ethnic groups, and clinical features of the disease (e.g., ocular vs. non-ocular involvement, active vs. quiescent disease). Anonymous blood samples (matched for race, age and sex) will be obtained from the NIH clinical center (CC) blood bank and will be compared to the diseased samples.