Ab1144 the Role of Systemic S100a4 Levels in Scleroderma as a Predictor of Treatment Response and Early Progression

Background: Our previous studies demonstrated that S100A4 is overexpressed in scleroderma (SSc) skin, fibroblasts, and preclinical models of SSc. Inactivation of S100A4 prevented dermal fibrosis induced by bleomycin and in Tsk-1 mice. Inhibition of S100A4 by murine mAbs (6B12) prevented the progression and induced regression of established dermal fibrosis induced by bleomycin. Objectives: The aim of this study was to assess the potential role of systemic S100A4 levels as a biomarker of SSc-related features and a predictor of treatment response and disease progression. Methods: Systemic levels of S100A4 were measured by ELISA (CUSABIO, Houston, USA) in 104 age-/sex-matched healthy controls (HC) and four different cohorts: 1)cross-sectional SSc patients (n=117; 67 lcSSc/50 dcSSc; mean age 55.8, disease duration 5.0 years); 2)SSc patients with active interstitial lung disease (ILD) treated with 6 (n=24) or 12 (n=16) months of iv cyclophosphamide; 3)SSc patients with progressive skin involvement and/or arthritis and/or ILD non-responsive to methotrexate/cyclophosphamide/mycophenolate treated with 2 (n=8) or 3 (n=16) 6-month cycles of rituximab; and 4)VEDOSS (Very Early Diagnosis of SSc) patients with Raynaud´s phenomenon who did not progress (n=15) or progressed (n=11) to SSc. Data are presented as median (IQR). Results: 1)S100A4 was significantly increased in SSc (67.2(43.1-88.7) vs. 51.1(35.9-60.8)ng/mL in HC;p<0.0001), especially in SSc with ILD (72.7(49.1-95.2) vs. 54.7(37.5-77.1)ng/mL in SSc without ILD; p=0.0124) and borderline with gastrointestinal involvement (69.3(50.3-96.7) vs. 63.1 (38.9-84.4)ng/mL without gastrointestinal involvement;p=0.0854). S100A4 was associated with lung function tests and borderline with disease duration (Table 1). 2)Treatment of active SSc-ILD with cyclophosphamide significantly decreased S100A4 over 6 months (76.3(52.9–98.6) vs. 73.2(44.4–98.6)ng/mL;p=0.013), whereas baseline S100A4 predicted the decrease in systemic inflammation (Table 1). 3)Treatment of progressive SSc (non-responsive to csDMARDs) with rituximab significantly decreased S100A4 over 6 months (83.7(70.4-109.6) vs. 81.5(60.2-100.4)ng/mL;p=0.0455). Baseline S100A4 predicted an improvement in hand function, fatigue, depression, and borderline in soilage, whereas a change in S100A4 was associated with function, quality of life, fatigue, and physical activity (Table 1). 4)Over an average of 3.5 years of follow-up in VEDOSS patients, S100A4 significantly decreased (p=0.0073) in non-progressors (13/15), whereas increased in 8/11 progressors (inter-group p=0.0429). S100A4 was associated with CRP and age in non-progressors and the titer of antinuclear antibodies in progressors (Table 1). Conclusion: Systemic S100A4 levels are elevated in SSc (especially in ILD), decrease with cs/bDMARD treatment, and predict the treatment response and progression to early disease. REFERENCES: NIL. Acknowledgements: Supported by MHCR023728. Disclosure of Interests: None declared.