Analysis of Autoantibodies against Promyelocytic Leukemia Nuclear Body Components and Biochemical Parameters in Sera of Patients with Primary Biliary Cholangitis.

Alicja Bauer,Damian Gawel,Paulina Wieszczy,Andrzej Habior

doi:10.3390/diagnostics11040587

Abstract

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by immune-mediated destruction of intrahepatic bile ducts and the presence of specific antibodies. The aim of the study was to examine the diagnostic significance of antibodies against promyelocytic leukemia nuclear body (PML NB) components such as Sp100, Sp140, and PML in a cohort of PBC patients and compare the results with biochemical and histological parameters. Serum samples were collected from 93 PBC patients. Anti-Sp100 and anti-PML antibodies were assessed using commercially available kits, anti-Sp140 using developed “in-house” ELISA test. Anti-Sp140, anti-Sp100, and anti-PML antibodies were present in 25 (27%), 37 (40%), and 29 (31%) PBC patients, respectively. Anti-PML NB positive patients also showed increased concentration of bilirubin and alkaline phosphatase (p < 0.05). In the group with the presence of at least two types of these antibodies, more frequent deaths or transplantations were observed. A correlation between the presence of antibodies and histological grade (OR = 2.55 p = 0.039) was established. Patients with bilirubin > 1.1 mg/dL at the time of diagnosis had a significantly shorter time of survival than patients with bilirubin ≤ 1.1 mg/dL (HR 5.7; 95% C.I., 2.7, 12.3; p < 0.001). Our data confirm very high specificity of anti-PML NB antibodies, which can expand the laboratory diagnostic capabilities of PBC. We found an association between positive reactivity of autoantibodies directed against components of PML nuclear bodies and higher concentrations of bilirubin and alkaline phosphatase, but the main prognostic marker of survival remains serum bilirubin.

Highlights

Introduction iationsPrimary biliary cholangitis (PBC) is a chronic, slowly progressive cholestatic liver disease, which is histologically characterized by portal inflammation and immune-mediated damage of the intrahepatic bile ducts [1,2,3,4]
Some studies have reported that nuclear body proteins are important targets of antinuclear antibodies (ANAs)
Data from Western and Southern Europe confirmed the importance of anti-Sp100 and anti-PML specific antibodies in PBC patients [17,21,24,27,33], to studies from North America [23]

Summary

Introduction

Primary biliary cholangitis (PBC) is a chronic, slowly progressive cholestatic liver disease, which is histologically characterized by portal inflammation and immune-mediated damage of the intrahepatic bile ducts [1,2,3,4]. Manifestation of several autoimmune features in patients with PBC has led to the generally accepted concept that the disease has an autoimmune pathogenesis [4,5,6]. PBC patients have autoantibodies directed against a variety of cellular components. Anti-mitochondrial antibodies (AMAs) are the most characteristic immunological feature of this entity [4,7]. Serum AMAs are present in more than 90% of PBC patients and 40–50% of PBC patients show antinuclear antibodies (ANAs) [8,9,10,11,12]. The ANA pattern in PBC includes multiple nuclear dots (MND-ANA)

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