CLINICAL SIGNIFICANCE OF NOVEL PBC AUTOANTIBODIES

描述（改编自应用程序） 原发性胆汁性肝硬化（PBC）是一种自身免疫性疾病， 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， 不明PBC的自然病程是缓慢进行性胆汁淤积 随着肝硬化和死亡的发展，除非患者接受肝脏移植， 移植然而，个体患者的疾病进展是 高度可变，症状前阶段可能持续20年以上。 由于PBC患者的病程不同， 对于这种疾病的新疗法，重要的是要确定预后 可能区分那些轻度疾病患者的因素（他们可能不会 需要治疗），从那些更具侵略性，快速进展， 病针对线粒体抗原的抗体存在于95%的 PBC患者。虽然抗线粒体抗体是敏感的， 特异于PBC的诊断，这些抗体的存在和滴度 不提供有关疾病严重程度和预后的信息。 大约40%的PBC患者具有针对 称为核体的核结构。核体是一个目标 由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），并在初步研究中，两个额外的核小体 鉴定出自身抗原（Sp140和Sp110）。至少有四个人 核体内的自身抗原表明， 针对这种结构的免疫是“抗原驱动的”。这些自身抗原可能是 鉴定患者中一种或多种病毒蛋白的细胞位置 在PBC。部件SP 140和SP 110的具体目标确定了 轻度PBC患者。来自370例明确定义队列的血清 患者将通过免疫印迹检测针对这些抗体的抗体。 2）鉴定核体内的其他自身抗原， 确定抗体的流行率和临床意义， 对这些蛋白质的抵抗。预计该 PBC患者病情严重程度抗体标志物的鉴定 将协助管理这些人。此外，识别 以及对核体新成分的表征， 深入了解该结构在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.