Brief Clinical Observation
Is prevalence of PBC underestimated in patients with systemic sclerosis?

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Abstract

Background

Clinically significant primary biliary cirrhosis occurs in 2.5% of patients with systemic sclerosis. Primary biliary cirrhosis-specific autoantibodies include anti-mitochondrial, anti-glycoprotein 210, and anti-sp100 antibodies. The majority of asymptomatic anti-mitochondrial-positive subjects express histological features of primary biliary cirrhosis. Early detection of primary biliary cirrhosis is important, as timely introduction of ursodeoxycholic acid may improve prognosis. The aim was to assess the prevalence of MIT3 IgG-anti-mitochondrial, gp210, sp100 and other autoantibodies in patients with systemic sclerosis and compare the clinical and biochemical parameters in those who are primary biliary cirrhosis-specific autoantibodies positive and negative.

Materials/methods

Fifty-two consecutive patients with systemic sclerosis were included. Thirty-three suffered from limited skin SS and 19 from diffuse SS.

Results

Eight (15%) patients with systemic sclerosis tested positive for primary biliary cirrhosis-specific autoantibodies. No significant differences were observed between primary biliary cirrhosis-specific autoantibodies positive and negative subjects in terms of various demographic, clinical or biochemical features. A trend towards increased prevalence of chronic fatigue in primary biliary cirrhosis-specific autoantibodies positive patients was observed.

Conclusions

Primary biliary cirrhosis-specific autoantibodies were detected in 15% of the systemic sclerosis patients. Since patients with primary biliary cirrhosis-specific antibodies are at high-risk or do suffer from primary biliary cirrhosis, screening for primary biliary cirrhosis-specific autoantibodies may be considered during routine assessment of systemic sclerosis.

Introduction

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver condition of presumed autoimmune aetiology frequently associated with other autoimmune diseases. Anti-mitochondrial antibodies (AMA) are serological markers of PBC and occur in up to 90–95% of patients [1]. In a proportion of patients, PBC may be both clinically and biochemically asymptomatic. It has also been shown that more than 90% of these asymptomatic subjects who are positive for AMA express histological features compatible with PBC [2]. Systemic sclerosis (SSc) is a chronic condition presenting itself with sclerosis of the skin and potential involvement of other organs including lung, kidney or gut. The prevalence of clinically significant PBC in patients with systemic sclerosis is estimated to be 2.5% [3]. Early detection of PBC is of clinical importance as timely introduction of the treatment with ursodeoxycholic acid (UDCA) makes the prognosis in this condition comparable to the general population [4]. Detection of AMA has been significantly improved by the recent introduction of new assays utilising the Gershwin-Leung recombinant MIT3 antigen containing the three major epitopes for AMA autoantibodies [5]. ELISA tests for detection of PBC-specific autoantibodies (AAB) to the nuclear pore complex glycoprotein 210 (anti-gp210) and the nuclear body associated-sp100 (anti-sp100) have also recently become available. While the sensitivity of anti-gp210 and anti-sp100 antibodies for PBC are in the range of 20–30%, both are highly specific for this condition (>99% for gp210 and >97% for sp100) [6], [7] and have been found in some PBC patients negative for AMA. In addition to their use in detecting some AMA-negative PBC patients, the presence of anti-gp210 antibodies in PBC patients has also been associated with more severe disease and unfavourable disease progression [8].

The aim of this study was to use newly developed ELISA assays to assess the prevalence of PBC-specific MIT3 IgG-AMA, gp210 and sp100 autoantibodies in a well-defined cohort of patients with SSc. We also compared clinical, biochemical, and serological parameters in PBC-specific AAB positive and negative SSc patients.

Section snippets

Materials and methods

Fifty-two consecutive patients with SSc referred to the Rheumatology Dept were included. Thirty-three suffered from limited skin SSc (lcSSc) and 19 from diffuse SSc (dcSSc). Only one patient in the cohort was diagnosed with PBC before inclusion into the study. Autoantibodies to MIT3 (AMA), gp210, sp100, centromere A&B (ACA), Scl-70, RNA Polymerase III, Ro-52, Ro-60, soluble liver antigen/liver pancreas (SLA/LP), F-actin, chromatin, and Jo-1 (histidyl-tRNA snythetase) were detected by ELISAs

Results

None of the patients had a family history of PBC. Eighteen (35%) patients suffered from other autoimmune conditions. These included 12 (23%) with autoimmune thyroiditis, 3 patients (6%) with Sjogren syndrome, 1 patient (2%) with both autoimmune thyroiditis and Sjogren syndrome, 1 patient (2%) with insulin dependent diabetes mellitus and 1 (2%) with rheumatoid arthritis.

Eight (15%) patients with SSc tested positive for PBC-specific autoantibodies (7 were M2 (MIT3) IgG and 1 was anti-sp100

Discussion

Systemic sclerosis and primary biliary cirrhosis are both chronic, presumed autoimmune conditions usually affecting middle age females. SSc can be associated with other autoimmune conditions. A recent study reported approximately one third of 118 SSc patients had 1 or 2 co-existing autoimmune diseases. The two most frequent diseases identified were autoimmune thyroiditis in 14.4% and primary Sjogren syndrome in 8.5% of the patients [9]. The prevalence of SSc in patients with PBC is estimated to

Conflict of interest statement

Gary L. Norman, Zakera Shums and Susan Encabo are employees of INOVA Diagnostics Inc.

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This study was accepted with distinction for poster presentation at DDW Meeting in Washington, May 2007.

1

These authors contributed equally to this work.

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