P123 Autoantibody profile and clinical associations in juvenile systemic sclerosis

Background/Aims Autoantibodies are valuable diagnostic and prognostic biomarkers in the systemic autoimmune/inflammatory disease systemic sclerosis (SSc) and associate with specific clinical phenotypes. Juvenile-onset SSc (JSSc) is very rare and studies investigating autoantibody profiles in children affected are sparse. This study aimed to assess autoantibody profiles and associated clinical presentations in JSSc patients. Methods 28 JSSc patients recruited to PAtient STratification & Individualised trEatment: Systemic sclerosis (PASTIES) study were analysed by Radio-IP, unidentifiable bands were characterised by mass spectrometry and associated clinical information described. Statistical analysis was performed using R version 4.5.1. Results Autoantibodies were detected in 25/28 (89%) of JSSc patients (Table 1). Anti-U1 positivity (n = 9) associated with overlap SSc (89% vs 37%, p = 0.016), lower risk for gastrointestinal (GI) involvement (11% vs 79%, p = 0.0012), fewer abnormal nailfold capillaroscopy results (56% vs 95%, p = 0.02), and arthritis (67% vs 16%, p = 0.01). Anti-PM-Scl (n = 5) associated with overlap disease (100% vs 44%, p = 0.04), interstitial lung disease (ILD) (80% vs 13%, p = 0.007) and diarrhoea (40.0% vs 0%, p = 0.02). Anti-Scl-70 (n = 5) was exclusively found in diffuse cutaneous SSc (dcSSc) cases (100% vs 17%, p = 0.001) and associated with more digital ulcers (40% v 0%, p = 0.04). Anti-U3 positivity (n = 5) associated with African American ethnicity (40% vs 0%, p = 0.027). Five patients had unknown bands on Radio-IP, identified as Regulator-of-chromosome-condensation-1 (RCC1) (n = 1) found in isolation, Argonaute1-4 (n = 2) co-occurring with anti-U1, and SNF2-Related-Chromatin-Remodelling-ATPase-5 (SMARCA5) (n = 2) co-occurring with anti-U3 and anti-PM-Scl. Conclusion We did not detect anti-centromere autoantibodies, and anti-U1 were the most common autoantibodies identified in this cohort, which links to the comparably high frequency of overlap disease in juvenile-onset disease. This study confirms association between autoantibody specificity and SSc subtype, particularly between anti-Scl-70 and dcSSc, and anti-U1/PM-Scl and overlap SSc. Autoantibodies targeting RCC1 and SMARCA5 were identified in JSSc for the first time. Anti-RCC1 has previously been identified in adult-onset SSc. Anti-AGO2/Su has previously been identified in several rheumatic diseases and is not associated with a particular disease subtype. Antibodies targeting SMARCA5, a component of the ISWI chromatin-remodelling complex, have not been reported before. Results confirm the importance of autoantibodies in JSSc and their use in guiding organ specific screening. Disclosure F.K. McMorrow: None. H. Lu: None. J. Fitzgerald: None. J.D. Pauling: Consultancies; John D Pauling has undertaken consultancy work, educational support and/or received speaker honoraria from Astra Zenaca, Boehringer Ingelheim, John & Johnson, IsoMab and CSL Vifor.. C. Hedrich: None. C.E. Pain: None. K.S. Torok: None. S.L. Tansley: None. S. Maltby: None. M. Elfadil: None.