Pos0615 clinical performance of a multiparametric autoantibody profile in systemic sclerosis patients

Background Systemic Sclerosis (SSc) is an autoimmune disease characterized by excessive fibrosis, inflammation and vasculopathy of the skin and internal organs. Interstitial lung disease (ILD) is the most important cause of mortality. Multiple autoantibodies (Abs) against nuclear proteins are present in >95% of patients. Anti-Topoisomerase-I (ATA), anti-CENP-B (ACA) and anti-RNA-polymerase-III (RNAP3) Abs are included in the 2013 SSc ACR/EULAR classification criteria. The detection of additional Abs is of interest to identify seronegative cases or specific clinical phenotypes. The particle-based-multi-analyte technology (PMAT) is a multiplexed system based on antigen covered paramagnetic particles with unique signatures. It allows to simultaneously obtain different autoantibody results. Objectives The aim of this study was to evaluate the clinical performance of PMAT-Aptiva in a cohort of SSc patients from Hospital Clínic de Barcelona. Methods Study cohort includes serum samples of patients with SSc (n=138), disease controls with other autoimmune diseases (n=205) and healthy blood donors (n=25). Demographic characteristics and clinical manifestations of patients were collected. SSc specific (ATA, ACA or RNAP3) or SSc associated (Ro52, U1-RNP, Ku, Th/To (Rpp25 and Rpp38), Fibrillarin, Pm/Scl, BICD2, MIT3, Mup44, PUF60 (isoforms 1, 2 and 6), RNPC3r, RNPC3 (peptide 1, 2, 3, 4 and 5), RuvBL1/2, SMN1 and TERF1) Abs were tested on Aptiva by PMAT technology (Werfen, San Diego, USA). The prevalence of Abs was measured based on the manufacturer’s recommended cut-offs. CTD-Essential has calibrated units (FLU) whereas other novel biomarkers were RUO (MFI). Associations between categorical variables were determined with Fisher’s exact test. The relative measure of an effect was expressed as the odds ratio and the 95% CI when considering Ab positivity as the exposure. Results with p values <0.05 were considered statistically significant. Results From SSc patients, 109/138 (79.0%) were positive for ACA (n=71; 51.4%), ATA (n=29; 21.0%), RNAP3 (n=7; 5.1%) or double positive ACA-ATA (n=2; 1.4%) Abs, while the remaining 29/138 (21.0%) were negative for these three Abs. Nineteen of the 29 (65.5%) negative patients were also negative for all tested novel biomarkers. In 10/29 (34.6%) either single or multi-positivity was observed for anti-Pm/Scl, U1-RNP, Th/To (Rpp25 and Rpp38), TERF1 and Ro52 Abs. Specificity for all SSc related biomarkers was over 93.0%. MIT3 and Ro52 were the most prevalent non SSc criteria Abs (17.4% and 16.6%, respectively). As expected, ACA, ATA and RNAP3 previously known associations with specific cutaneous phenotype and ATA and RNAP3 with the presence of ILD were confirmed (Table 1). Interestingly, Rpp38 and RuvBL1 were more frequently found in patients with ILD. Additionally, PUF60 isoform 6 was associated with the presence of diffuse cutaneous phenotype whereas TERF1 was more prevalent in patients with diastolic dysfunction. We did not find association between any of the Abs studied and neoplasia, cardiac arrhythmias or conduction disturbances, pericarditis or myocardial damage, myositis, pulmonary hypertension or esophageal motility disorders. Conclusion In our SSc cohort, PMAT-Aptiva showed a proper specificity and represents a suitable option for patients’ evaluation. Confirmation of promising clinical associations for novel markers PUF60 (isoform 1 and 6), FHL1, RuvBL1 and TERF1 in larger SSc cohorts is warranted. Table 1. Significant associations (odds ratio) between clinical manifestations and markers. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.