December 12/10: Diagnostic utility of anti-Ro52

Objectives To determine the prevalence and diagnostic utility of monospecific anti-Ro52 (defined as an immune response against Ro-52 antigen in the absence of reactivity to Ro-60 antigen) reactivity in selected autoimmune diseases. Study design Stored diagnostic non-consecutive serum samples obtained from patients with systemic lupus erythematosus (SLE), primary Sjogren’s syndrome (pSS), systemic sclerosis, idiopathic inflammatory myopathies (IIM), rheumatoid arthritis, primary biliary cirrhosis and mixed essential cryoglobulinaemia were analysed by line immunoassay to detect the presence of anti-Ro52 and other autoantibodies. Results Monospecific anti-Ro52 reactivity was found in 51 (12.7%) of the 402 samples tested. Anti-Ro52 was the most common serological marker in patients with IIM (35/147, 23.8%) and co-occurred with anti-Jo1 (10/18, 55.6%; p1⁄40.02). The prevalence of anti-Ro52 reactivity was significantly more than anti-Ro60 reactivity in patients with IIM, systemic sclerosis, primary biliary cirrhosis, mixed essential cryoglobulinemia and pSS. The mean signal intensity of anti-Ro52 reactivity was significantly higher in pSS than SLE and associated with rheumatoid factor positivity. The mean signal intensity of anti-Ro52 correlated with anti-Ro60 and anti-La in pSS and SLE. Conclusions Monospecific anti-Ro52 reactivity is not disease specific but may be of importance in patients with IIM. Furthermore, as anti-Ro52 reactivity is more prevalent than anti-Ro60 reactivity in certain autoimmune conditions, specific testing for their distinction in clinical practice is recommended. INTRODUCTION Autoantibodies to Ro-52 are not disease specific and are prevalent in many systemic autoimmune diseases including systemic lupus erythematosus (SLE) and primary Sjogren’s syndrome (pSS). The diagnostic utility of ‘monospecific’ or ‘isolated’ anti-Ro52 autoantibodies (anti-Ro52 reactivity without concomitant anti-Ro60 reactivity) is controversial 2 and has been shown to have low diagnostic value in evaluation of autoimmune diseases. Recent evidence for their clinical relevance comes from a study in patients with idiopathic inflammatory myopathies (IIM), where anti-Ro52 autoantibodies were the most common immune marker detected and associated with a favourable response to prednisone. The Ro-52 antigen is a member of the RING/Bbox/coiled-coil tripartite motif protein and induces cellular events through ubiquitination. 11 In contrast, the Ro-60 antigen binds to misfolded non-coding RNAs and tags them for degradation. It has been proposed that detection of single reactivity to Ro-60 and Ro-52 is desirable as they represent two distinct functional autoantibody systems. The prevalence of anti-Ro52 autoantibodies without anti-Ro60 has been reported to be 1% of all antinuclear antibody (ANA) positive sera. Since anti-Ro52 autoantibodies are not disease specific, we sought to determine their prevalence in various selected autoimmune diseases, as opposed to testing serial laboratory samples sent for detection of antibodies to extractable nuclear antigens (ENAs), which has been reported to be of limited clinical value. The aims of our study were to determine the prevalence and diagnostic utility of detecting monospecific anti-Ro52 (defined as an immune response against Ro-52 antigen in the absence of reactivity to Ro-60 antigen) reactivity in selected systemic autoimmune diseases by the Euroline ANA profile line immunoassay and its correlations with other serological markers. METHODS Design This cross-sectional observational study was conducted at the Flinders Medical Centre, Adelaide, South Australia, during the period September to December 2007. Stored non-consecutive diagnostic serum samples (n1⁄4402) obtained from patients with SLE (n1⁄467), pSS (n1⁄440), systemic sclerosis (SSc, n1⁄4106), IIM (n1⁄4147), rheumatoid arthritis (RA, n1⁄419), primary biliary cirrhosis (PBC, n1⁄414), mixed essential cryoglobulinaemia (MEC, n1⁄49), and controls (n1⁄415, patients with insect venom allergy but otherwise healthy and with no autoimmune diseases) were analysed by line immunoassay (LIA, Euroline ANA profile assay, Euroimmun AG, Luebeck, Germany) to detect the presence of autoantibodies against different ENAs as described below, with a focus on anti-Ro52 autoantibodies. The study patients were attending the private and public hospital rheumatology clinics in the region and their diagnosis was confirmed by review of medical records and laboratory results in accordance with the current classification criteria being used. All patients with IIM had a positive muscle biopsy and were further classified as polymyositis (PM), dermatomyositis and inclusion body myositis based on their clinical features, histopathology and investigations. The stored serum samples were part of ongoing research projects investigating the epidemiology, clinical features and serology of systemic autoimmune diseases for which ethics approval has been obtained from Royal Adelaide Hospital, Adelaide, Australia Flinders Medical Centre, Adelaide, Australia Correspondence to Dr Manish Dugar, Department of Rheumatology, Level 4 Eleanor Harrald Building, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5042, Australia; manish.dugar@ health.sa.gov.au Received 17 August 2009 Accepted 11 October 2009 Postgrad Med J 2010;86:79e82. doi:10.1136/pgmj.2009.089656 79 Original article group.bmj.com on April 12, 2010 Published by pmj.bmj.com Downloaded from