Abstract

Anti-SS-A antibodies are often sought for in autoimmune diseases diagnosis. Two different target proteins have actually been identified: Ro52 and Ro60. Clinical and immunological associations seem different depending on anti-Ro52 or anti-Ro60 antibodies presence. However, due to a heterogeneous presentation in the literature, some immunology laboratories in France have stopped providing anti-Ro52 antibody findings. We report here a new hospital study designed to determine the diagnostic utility of the separate detection of anti-Ro52 and anti-Ro60 antibodies. We conducted a retrospective, observational study, including every adult patient with positive antinuclear antibodies (ANA) tested in our immunology laboratory, and associated with anti-Ro52 and/or anti-Ro60 antibodies, between 2011 and 2014. Out of 13032 sera tested for ANA, 399 adults had antibodies to Ro52 and/or Ro60; 81.7% were female, with a mean age of 54.5 ± 17.0 years. Anti-Ro52 antibodies were found in 75.7% of the patients and anti-Ro60 antibodies in 56.9%. Among them, 43.1% were classified in the Ro52 + Ro60- group, 32.6% in the Ro52 + Ro60 + group and 24.3% in the Ro52-Ro60+ group. In the Ro52-Ro60+ group, systemic lupus was the most frequent diagnosis (48.5%), with a possible association with antiphospholipid antibodies (anti-cardiolipin antibodies: OR 2.5 (CI95 [1.0–5.0], p = 0.05) and lupus anticoagulant {OR 3.6 (CI95 [1.10–10.0] p = 0.02)}. In the Ro52+Ro60+, primary Sjögren Syndrome was the most likely (OR 4.2 95% CI [2.1–8.3] p < 10−4), especially in patients Ro52+Ro60+La+. Patients with isolated anti-Ro52 had a wider variety of diseases associated, but among auto-immune diseases they were more prone to inflammatory myositis (OR 10.5 [1.4–81.7], p = 0.02) and inflammatory rheumatism (OR 4.6 [1.6–13.8], p = 0.006) in contrast to systemic lupus (OR 0.2 [0.1–0.3], p < 10−4) or primary Sjögren's syndrome (OR 0.1 [0.06–0.2], p < 10−4). We therefore suggest that, when anti-ENA antibodies are prescribed, it should include separate anti-Ro52 and anti-Ro60 antibodies determination. To go even further, we would like to suggest a change in ENA nomenclature to avoid confusion, abandoning the anti-SS-A label in favor of the anti-Ro52/TRIM21 or anti-Ro60 antibody for a clearer designation.

Highlights

  • Antibodies to the Ro/SS-A system are classically described in association with autoimmune diseases (AID) such as systemic lupus, and Sjögren’s syndrome [1]

  • Ro52 corresponds to TRIM21, belonging to the Tripartite Motif Protein (TRIM) family [4]

  • Some authors suggest that detection of Ro60 Ab alone is sufficient for AID diagnosis. Based on these heterogeneous data, some immunology laboratories in France no longer test for Ro52 antibodies (Ro52 Ab) or, at least, do not report the results of its detection. This can be confusing for clinicians as they often do not clearly know what has been tested for, when receiving an “anti-SS-A antibodies” result

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Summary

Introduction

Antibodies to the Ro/SS-A system are classically described in association with autoimmune diseases (AID) such as systemic lupus, and Sjögren’s syndrome [1]. Two different target proteins have been differentiated: Ro60 (60 kDa) and Ro52 (52 kDa), that have distinct biochemical and immunological functions [2, 3]. Ro52 corresponds to TRIM21, belonging to the Tripartite Motif Protein (TRIM) family [4]. It is implicated in protein ubiquitination, pro-inflammatory states (interleukin 2) and apoptosis mechanisms [4,5,6,7]. It seems to have an important function in cell survival after ultraviolet irradiation [8]

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