Ab0822 systemic sclerosis associated antibodies positivity in systemic sclerosis patients: single vs. combination

Background Autoantibodies (abs) are one of the most widely used tools currently in systemic sclerosis (SSc) as biomarkers. It has been described that 95% of patients with SSc have at least one ab and ≈5% >1. When looking only at abs associated with SSc (SSc-ab) that prevalence is reduced to 2.6%. The combination usually confers different clinical characteristics compared to those with positivity for a single ab. Objectives To determine the prevalence of the combination of SSc-ab in a series of patients diagnosed with SSc, and to analyze the clinical differences between those with positivity for a single vs multiple SSc-ab. Methods Retrospective study of 134 patients with SSc in whom the SSc-ab profile was systematically determined by an immunoblot (Euroimmun®) which included anti-topoisomerase (ATA), anti-centromere (ACA), anti RNA-Polymerase III (ARA), anti-U3-RNP (U3), anti-Th/To (Th/To), anti-Ku (Ku), anti-PmScl (PmScl) and anti-U1-RNP (U1) abs. Demographic and clinical differences were studied between those with positivity for a single ab vs those with more than one. Differences were identified using Fisher’s exact test, and Mann-Whitney. Results Table 1 shows the SSc-ab profile of our patients: 128/134 (96%) were ANA+, 111 (82%) had 1 SSc-ab, 8 (8%) had 2 and 3 (2.3%) had 3 concomitant SSc-ab. Ku was found in combination with other ab in all patients and was present in the 3 patients with 3 ab. When analyzing patients with combined vs sole abs, we found the following statistically significant differences: the limited cutaneous SSc subtype associated with ACA was lost in the combinations ACA-U1-Ku+ and ACA-Ku+, being 0/1 patients (0%, p=0.038) and 0/1 patients (0%, p=0.039), respectively). Patients with ATA-ARA+ had a higher modified Rodnan skin score vs ATA+ (18.33 ± 2.08 vs 9.67 ± 5.59, p=0.036). No other statistically significant differences were found in any other characteristics in the patients with ≥1 vs 1 ab, although a trend toward some clinical differences was seen in ACA-U1-Ku+ patients, with more digestive symptoms and interstitial lung disease, and less myositis than ACA+. Additionally, patients ACA-PmScl-Ku+ seemed to have less myositis than those with PmScl+, and patients ACA-Ku+ less myositis than those ACA+. Conclusion The concomitant presence of more than 1 SSc-ab is more frequent in our cohort than initially described (8%), likely due to the systematic detection carried out in our study. Anti-Ku was the most frequent ab in combination to others. The combination of abs may change the characteristic clinical phenotypes associated to them when found in isolation. We saw some differences in our study, although conclusions cannot be drawn due to the limiting sample size. The implementation of routine immunoblots as ab screening to achieve a better characterization of patients could be a helpful tool for medical professionals, as these combinations of SSc-ab may have prognostic implications. References [1]Stochmal, A. et al . Antinuclear Antibodies in Systemic Sclerosis: an Update. Clin. Rev. Allergy Immunol. 58 , 40–51 (2020). [2]Clark et al . Combinations of scleroderma hallmark autoantibodies associate with distinct clinical phenotypes. Sci. Rep. 12 , 1–8 (2022). Table 1 : Profile of antibodies. Numbers in brackets indicate total number of patients. Total Coexistence % Overlapping antibodies 2 3 Anti-Ku (Ku) 5 5 100% ATA (1), ACA (1) PmScl-ACA (1), U1-ACA (1), Th/To-U1 (1) Anti-U1-RNP (U1) 4 2 50% - ACA-Ku (1), Th/To-Ku (1) Anti-Th/To (Th/To) 4 2 50% ACA (1) U1-Ku (1) Anti-PmScl (PmScl) 7 3 43% ATA (1), ACA (1) ACA-Ku (1) Anti-topoisomerase (ATA) 22 5 23% ARA (3), PMScl (1), Ku (1) - Anti-RNApolymerase III (ARA) 13 3 23% ATA (3) - Anti-centromere (ACA) 61 5 8% PmScl (1), Th/To (1), Ku (1) U1-Ku (1), PmScl-Ku (1) Anti-U3-RNP 1 0 0% - - Acknowledgements Project “202022-33” is funded by FUNDACIÓ LA MARATÓ DE TV3 Disclosure of Interests None Declared.