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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;pConclusion: 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.
Štorkánová et al. (Sat,) studied this question.