SAT0031 Anti-RO52 autoantibody epitope mapping in european cohort of myositis patients
Authors: O. Krystufkova, V. Dzikatite, P.J. Charles, H.F. Mann, L. Ekholm, M. Vincze, I. Putova, N. Kasprikova, L. Padyukov, K. Danko, P. Novota, J. Vencovsky, M. Wahren-Herlenius, I.E. Lundberg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The most frequent myositis associated autoautoantibodies are directed to Ro52-kd protein (12-26%). Antibodies to the immunodominant epitope (p200) of Ro52 are associated with SLE and Sjögren's syndrome (SjS) with suggestion for a pathogenic effect in development of neonatal heart block. The role of anti-Ro52 autoantibodies in myositis is not clear. Presence of anti-Ro52 in combination with anti-Jo-1 autoantibodies is associated with interstitial lung disease (ILD). <h3>Objectives</h3> The aim was to investigate the associations of reactivity to Ro52 epitopes with disease manifestations, autoantibody profile, smoking status and HLA-DRB1 alleles in myositis. In order to test the hypothesis of epitope spreading the association of disease duration with polyreactivity was evaluated. <h3>Methods</h3> Serum samples from 468 myositis patients were collected in three countries: Czech (n=133); Hungary (n=202), Sweden (n=133). The reactivity with recombinant full length (FL) Ro52 antigen, its four deletion fragments (Ro52-3,-4,-5 and -6) and 7 overlapping synthetic peptides (p136-200) covering the major immunodominant region (Ro52-3) was measured by ELISA. Autoantibodies to Jo-1, PL-7, PL-12, EJ, OJ, SRP, PM-Scl, Ku, Mi-2β, U1-RNP were detected by LIA. 417 patients were genotyped for HLA-DRB1. Smoking status was known in 434 patients. <h3>Results</h3> 184 patients with dermatomyositis (DM), 250 polymyositis (PM), 11 inclusion body myositis, 20 juvenile DM/PM and three with mixed connective tissue disease were included in the analysis. Median disease duration was 4.7 (0-41.5) years. ILD was present in 132 (29%) of patients. In total 175 (40%) patients were smokers. Reactivity to Ro52-FL was present in 97 (21%) samples; 87 (90%) of these showed specificity to Ro52-3 and anti-p176 dominated (66; 76%) whereas only 44 (51%) had reactivity to the p200 epitope. Anti-Ro52FL positivity was associated with presence of ILD (OR 3.8; p&lt;0.0001), anti-Jo1 (OR=9.0; p&lt;0.0001) and HLA-DRB1*03 allele (OR=1.9; p=0.009). No significant epitope associations were detected. No association was found between reactivity to Ro52 or polyreactivity to 2 or more fragments or peptides and disease duration or smoking status. Moreover, there was no additional effect of smoking to association with HLA-DRB1*03 allele. <h3>Conclusions</h3> Our results confirm the association between anti-Ro52 positivity with ILD, anti-Jo-1 autoantibodies and HLA-DRB1*03 allele in myositis. The dominance of reactivity to epitope p176 in myositis patients differs from dominant p200 in SLE and SjS, but its clinical significance is not clear. There was no effect of smoking or evidence for epitope spreading in anti-Ro52 response. Supported by EU 6.FP integrated project AutoCure LSHB CT-2006-018661 and Grant NT 12438 of IGA MZCR <h3>Disclosure of Interest</h3> O. Krystufkova Grant/Research support from: EU 6.FP integrated project AutoCure LSHB CT-2006-018661 and Grant NT 12438 of IGA MZCR, V. Dzikatite: None Declared, P. Charles: None Declared, H. Mann: None Declared, L. Ekholm: None Declared, M. Vincze: None Declared, I. Putova: None Declared, N. Kasprikova: None Declared, L. Padyukov: None Declared, K. Danko: None Declared, P. Novota: None Declared, J. Vencovsky: None Declared, M. Wahren-Herlenius: None Declared, I. Lundberg: None Declared