ReviewClinical significance of anti-Ro52 (TRIM21) antibodies non-associated with anti-SSA 60 kDa antibodies: Results of a multicentric study
Introduction
Antibodies to SSA antigen (Ro52/Ro60), historically described as a marker for Sjögren syndrome and systemic lupus erythematosus are now known not to be directed to the same macromolecular complex [1]. It is well admitted that Ro52 and Ro60 (SSA) antigens consisted of two different proteins coded by distinct cDNAs [2], [3]. The Ro52 gene has been mapped to the end of the short arm of human chromosome 11 [4] and Ro52 antigen has recently been identified as TRIM21 protein, belonging to the tripartite motif (TRIM) protein family. Indeed, the 52 kDa Ro antigen is identified as a family member of the RING/Bbox/coiled-coil (RBCC) tripartite motif protein and as an ubiquitin ligase that is over expressed in peripheral blood of mononuclear cells in Sjögren syndrome and SLE patients [5], [6]. So, anti-Ro52 antibodies are named anti-TRIM21 antibodies and the clinical significance of anti-Ro52/TRIM21 antibodies remains controversial, because some non-immunological interactions may exist between TRIM21 protein and human IgG [7]. Anti-Ro60 (SSA) and anti-Ro52 (TRIM21) represent two distinct autoantibodies systems. Whereas Ro52 has an extraordinary immunogenicity [8] and may be the most antigenic protein recognized in humans, separate detection is desirable in a clinical diagnostic setting [1], [9]. Clinically, the presence of anti-Ro52 antibodies has been reported in a wide variety of diseases. In autoimmune diseases, the frequency of anti-Ro52 antibodies is high in myositis, Systemic sclerosis [10] but also in autoimmune liver diseases [11], [12]. These antibodies also tend to be associated with non-autoimmune diseases such as viral infections or neoplastic diseases [13].
The aim of this multicentric study was to investigate the clinical significance of anti-Ro52 (TRIM21) antibodies in patients recruited from various departments of medicine and displaying anti-Ro52 but not anti-SSA/Ro60 antibodies.
Section snippets
Inclusion criteria
In this retrospective multicentric study, patients were selected on the basis of two criteria: (i) the presence of antibodies to TRIM21/Ro 52 and the absence of anti-SSA/Ro60 antibodies in serum and (ii) knowledge of their medical status determined from their medical records.
Antibodies detection
During 18 months, consecutive sera were selected by each of the 10 laboratories through auto-immunity exploration using its own method, ELISA, immunodot or Luminex technology, reported in Table 1. The sera were checked for a
Results
Among the 247 tested sera, only sera confirmed as anti-Ro52 positive and anti-SSA/Ro60 negative were later analyzed. Non-selected sera were divided into two groups in relation with the primary test:
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not enough sensitivity for Ro60: sera were finally Ro52 and Ro60 positive.
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too sensitive for Ro52: sera were finally Ro52 and Ro60 negative.
After confirmation, data from 155/247 (63%) patients were studied: 131 women (85%) and 24 men (15%), mean age: 51.7 ± 17 years (range 13–88). These sera were
Discussion
In this study, we looked at the clinical relevance of anti-Ro52/TRIM21 antibodies in autoimmune and non-autoimmune diseases. This multicentric retrospective study was performed with the results of autoimmunity tests in different laboratories in various hospitals. Then, in our recruitment, we had a high prevalence of autoimmune diseases (73%) and our results differ from published series [13], [14] in which Anti-Ro52 was not consistently associated with autoimmune disease and weakly predictive
Conclusion
Beside tRNA-antisynthetases syndrome, it will be helpful to test anti-Ro52 antibodies in pulmonary infections for the diagnosis of idiopathic pneumopathies. Further investigations should be useful to determine the clinical interest of anti-Ro52 determination in the diagnosis of related antisynthetase syndrome, without classical antibodies or to classify as autoimmune idiopathic interstitial lung disease.
Take-home messages
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Ro52 (TRIM21) is distinct from Ro60 (SSA) antigen.
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Anti-Ro52 and anti-Ro60 (SSA) should be tested separately.
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Anti-Ro52 antibodies are detected preferentially in autoimmune diseases.
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Anti-Ro52 antibodies are often present when patients develop lung infections, even in the absence of tRNA antisynthetase antibodies.
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Presence of anti-Ro52 antibodies should probably precede development of autoimmune disease and must induce sequential follow-up of positive patients.
Acknowledgements
We thank François Lopez and the autoimmunity team from Bio-Rad Laboratories for support with the tests on BioPlex® and all the physicians who contributed to this study.
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