Is there an association between Ro52/TRIM21 antibodies and rheumatoid factor in systemic sclerosis?

Abstract

Autoantibodies to Ro52/TRIM21 are among the most common autoantibodies detected in subjects with systemic autoimmune rheumatic autoimmune diseases (SARD), including systemic sclerosis (SSc) [1–3]. Ro52/TRIM21 is an immunoglobulin-binding protein [4]. It is also an extraordinarily prevalent and antigenic target of autoantibodies. It is part of the Ro/SSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. Recently, it has been shown that Ro52/TRIM21 plays a major role in the destruction of misfolded IgG1. Its C-terminal PRYSPRY domain, also known as B30.2 domain, has been found to be of great importance for its function as a highly specific IgG receptor. Studies have suggested a possible association between anti-Ro52/ TRIM21 antibodies and rheumatoid factor (RF) in Sjogren’s syndrome (SjS) [5, 6]. In a cohort of 187 SjS patients, 37 % were anti-Ro52/TRIM21 positive and 74 % had significantly high RF titers [5]. Similarly, in another study, the prevalence of anti-Ro52/TRIM21 varied from 14.1 % (n = 106) in SSc patients to 97.5 % (n = 40) in SjS, and the mean anti-Ro52/TRIM21 signal intensity was significantly higher in SjS patients who were RF positive [6]. The presence of RF in SSc patients has been described in several studies with a frequency that varies from 12 to 37 % [7–9] and higher in selected SSc subjects (66 % in subjects with rheumatoid arthritis overlap and 59 % in subjects with SjS overlap) [10]. Taking these reports into account, we set out to determine if there was an association between Ro52/TRIM21 and RF in SSc. Sera from 89 anti-Ro52/TRIM21 antibody positive and 89 antibody negative SSc subjects from the Canadian Scleroderma Research Group cohort were selected consecutively. Anti-Ro52/TRIM21 antibodies were detected by an addressable laser bead immunoassay (ALBIA) utilizing a commercially available kit (QUANTAPlex ENA 8, INOVA Diagnostics Inc., San Diego, CA) in a Luminex 100 (Luminex Corp., Austin, TX) platform, the results of which were cross-validated on another kit (Connective13, BMD/FIDIS, Paris, France) in a Luminex 200 (Luminex Corp.) platform, according to protocols previously described [2]. The sera of all study subjects were tested for IgM RF by ELISA (INOVA, San Diego, CA) using a cutoff value for RF set according to the manufacturer’s recommendations at 6 IU/ml. Descriptive statistics and logistic regression were used to analyze the data, using SAS v.9.2 (SAS Institute, USA). After excluding 4 subjects with incomplete datasets, 86 Ro52/TRIM21 autoantibody positive and 88 Ro52/ TRIM21 antibody negative subjects were available for this analysis (Table 1). The overall prevalence of RF was high (45 %), but there was no difference in either Ro52/ The Investigators of the Canadian Scleroderma Research Group is given in ‘‘Appendix’’.