SAT0347 AUTOANTIBODIES TO UNCOUPLED RO52 PROTEIN IN PATIENTS WITH ANTI-SYNTHETASE SYNDROME; A POTENTIAL MARKER FOR SUBCLASSIFICATION.
Authors: A. Yoshida, Y. Okazaki, T. Gono, M. Kuwana
Journal: Annals of the Rheumatic Diseases (2020)

Background: Anti-Ro/SS-A (anti-SS-A) antibody is one of myositis-associated antibodies, and is found in patients with anti-synthetase antibodies 1 . Anti-SS-A antibody targets the complex consisting of Ro52 and Ro60 proteins coupled with cytoplasmic non-coding Y-RNAs. Autoantibody against Ro52 uncoupled with Y-RNAs (anti-uncoupled Ro52) is also present in patients with a variety of connective tissue diseases, including myositis 2 . However, the majority of previous studies used enzyme-linked immunoassay (EIA) for detection of anti-Ro52 antibodies, resulting in failure to discriminate between anti-Ro52 antibodies coupled and uncoupled with Y-RNAs. The prevalence and clinical significance of anti-uncoupled Ro52 antibodies still remain unclear in patients with anti-synthetase antibodies. Objectives: To elucidate clinical relevance of anti-uncoupled Ro52 antibodies in a cohort of anti-synthetase syndrome employing RNA immunoprecipitation assay (RNA-IP) in combination with EIA. Methods: This is a single-center, cross-sectional study involving 80 patients positive for anti-synthetase antibodies by RNA-IPP. Complete clinical information was obtained from a medical chart review. Serum samples were obtained at first visit and stored at -20°C until use. Anti-SS-A and anti-SS-B antibodies were detected by RNA-IP, and anti-Ro52 and anti-Ro60 antibodies were measured by commercial EIA kits (ORGENTIC, Mainz, Germany). Autoantibodies that immunoprecipitated Y-RNAs regardless of results of anti-anti-Ro52 or anti-Ro60 EIAs were regarded as anti-SS-A antibody, while antibodies that did not immunoprecipitate Y-RNAs but reacted with anti-Ro52 antibodies by EIA were regarded as anti-uncoupled Ro52 antibody. Student’s t-test, Mann-Whitney’s U test, and Fisher’s exact test were employed to compare the clinical features between each group. Cumulative survival rates were compared using log-rank test. Results: In our cohort of 80 patients with anti-synthetase antibody, mean age at diagnosis was 61 ± 12 years, and 76% were female. Clinical diagnosis was classic dermatomyositis (cDM) in 11, clinically amyopathic dermatomyositis (CADM) in 21, polymyositis (PM) in 11, systemic sclerosis (SSc) in 3, myositis-SSc overlap in 5, interstitial lung disease (ILD) alone in 29, and unclassified in 3. The antigenic specificity of anti-synthetase antibodies included Jo-1 in 19, PL-7 in 12, PL-12 in 9, EJ in 21, OJ in 4, and KS in 16. Anti-SS-A anti-SS-B antibodies were found in 14 (17%) and 2 (2.5%) patients, respectively. The presence of anti-Ro60 and anti-SS-A antibodies was almost concordant (P &lt; 0.0001), although the presence of anti-Ro52 and anti-SS-A antibodies was not correlated (P = 0.8). This was primarily because of high prevalence (40%) of autoantibodies to uncoupled Ro52. Interestingly, prevalence of anti-uncoupled Ro52 antibodies was different among antigenic specificities of anti-synthetase antibodies: high in Jo-1 (58%) and EJ (55%), and low in PL-7 (8%) and OJ (0%). Gottron’s sign/papule was more frequent in patients with anti-uncoupled Ro52 than in those without (61% versus 28%, P = 0.005), resulting in clinical diagnosis of cDM or CADM more common in patients with anti-uncoupled Ro52 than in those without (59% versus 26%; P = 0.003). The prevalence and extent of ILD tended to be greater in anti-uncoupled Ro52-positive versus negative patients, but difference did not reach statistical significance. There were no differences in cumulative survival rates between patients stratified by the presence or absence of anti-uncoupled Ro52 antibodies. Conclusion: Autoantibodies to uncoupled Ro52 were commonly found in patients with anti-synthetase antibodies. Anti-Ro52 positivity might be useful for subclassifying anti-synthetase syndrome. References: [1]McHugh NJ et al. Nat Rev Rheumatol . 2018; 14 (5): 290-302. [2]Schulte-Pelkum J et al. Autoimmun Rev . 2009; 8 (7): 632-7. Disclosure of Interests: Akira Yoshida: None declared, Yuka Okazaki: None declared, Takahisa Gono Speakers bureau: Astellas, and Medical and Biological Laboratories, Masataka Kuwana Grant/research support from: Acetelion, Consultant of: Acetelion, Bayer, Chugai, Corbus Pharmaceuticals, CSL Behring and Reata Pharmaceuticals. He was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim)