CLINICAL SIGNIFICANCE OF NOVEL PBC AUTOANTIBODIES

描述（改编自应用程序）

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.