CLINICAL SIGNIFICANCE OF NOVEL PBC AUTOANTIBODIES

说明(改编自应用程序) 原发性胆汁性肝硬变是一种自身免疫性疾病，主要表现为 影响肝内胆管。与许多其他自身免疫性疾病一样， 绝大多数PBC患者是女性，这种疾病的病因 是未知的。PBC的自然历史是一种缓慢进行性的胆汁淤积。 随着肝硬变的发展和死亡，除非患者接受肝脏检查 移植。然而，单个患者的疾病进展是 高度变数和症状前阶段可能持续20年以上。 由于PBC患者的病程多种多样，而且可获得 对于这种疾病的新治疗方法，重要的是确定预后 可能区分那些患有轻度疾病的患者的因素(谁可能不是 需要治疗)，来自那些更具侵袭性的、进展迅速的 生病了。95%的人存在针对线粒体抗原的抗体 PBC患者的比例。尽管抗线粒体抗体是敏感的和 这些抗体的存在和滴度对PBC的诊断具有特异性 不提供有关疾病严重程度和预后的信息。 大约40%的PBC患者有针对A基因的抗体 称为核体的核结构。核物体是 多种病毒在急性感染过程中产生的蛋白质。 以前的研究人员在核体内发现了两种自身抗原 (Sp100和PML)，在初步研究中，另外两个核体 鉴定了自身抗原(Sp140和Sp110)。至少有四个人在场 核体内的自身抗原表明免疫反应直接 对抗这种结构是“抗原驱动的”。这些自身抗原可能是 确定患者体内一种或多种病毒蛋白的细胞位置 与PBC合作。组件Sp140和Sp110的特定目的标识了 患有轻度PBC的患者。来自370名定义明确的队列的血清 患者将通过免疫印迹法检测针对这些病毒的抗体。 蛋白质；2)识别核体内的其他自身抗原和 检测定向抗体的流行率及临床意义 在PBC患者中对抗这些蛋白。据预计， PBC患者病情严重程度抗体标志物的鉴定 将协助管理这些个人。此外，身份识别 对核体的新成分的表征将提供 洞察这种结构在PBC发病机制中的作用。

DESCRIPTION (adapted from the application) Primary biliary cirrhosis (PBC) is an autoimmune disease that predominantly affects intrahepatic bile ducts. As with many other autoimmune diseases, the vast majority of patients with PBC are women and the etiology of this disorder is unknown. The natural history of PBC is one of slowly progressive cholestasis with the development of cirrhosis and death unless the patient undergoes liver transplantation. Disease progression in an individual patient, however, is highly variable and a pre-symptomatic phase may last longer than 20 years. Because of the variable course of patients with PBC and the availability of novel treatments for this disease, it is important to identify prognostic factors that may distinguish those patients with mild disease (who may not require treatment) from those with a more aggressive, rapidly progressive illness. Antibodies directed against mitochondrial antigens are present in 95% of patients with PBC. Although anti-mitochondrial antibodies are sensitive and specific for the diagnosis of PBC, the presence and titer of these antibodies do not provide information concerning disease severity and prognosis. Approximately 40% of patients with PBC have antibodies directed against a nuclear structure known as the nuclear body. The nuclear body is a target of proteins produced by a variety of viruses during the course of acute infection. Previous investigators identified two autoantigens within the nuclear body (Sp100 and PML) and in preliminary studies, two additional nuclear body autoantigens (Sp140 and Sp110) were identified. The presence of at least four autoantigens within the nuclear body suggests that the immune response directed against this structure is "antigen-driven". These autoantigens may be identifying the cellular location of one or more viral proteins in patients with PBC. The specific aims of components Sp140 and Sp110 identify a subset of patients who have a mild form of PBC. Serum from a well-defined cohort of 370 patients will be tested by immunoblot for antibodies directed against these proteins; 2) Identify additional autoantigens within the nuclear body and determine the prevalence and clinical significance of antibodies directed against these proteins in patients with PBC. It is anticipated that the identification of antibody markers of disease severity in patients with PBC will assist in the management of these individuals. In addition, identification and characterization of novel components of the nuclear body will provide insight into the role of this structure in the pathogenesis of PBC.