AB1144 THE ROLE OF SYSTEMIC S100A4 LEVELS IN SCLERODERMA AS A PREDICTOR OF TREATMENT RESPONSE AND EARLY PROGRESSION
Authors: H. Štorkánová, L. Andres Cerezo, S. Oreska, A. Jirankova, A. Bobrova, K. Bobrova, B. Heřmánková, J. Klingelhöfer, R. I. Hussain, J. Hallén, J. Distler, K. Pavelka, L. Šenolt, J. Vencovský, R. Bečvář, M. Tomčík
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> 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. <h3>Objectives:</h3> 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. <h3>Methods:</h3> 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). <h3>Results:</h3> 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&lt;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). <h3>Conclusion:</h3> 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. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Supported by MHCR023728. <h3>Disclosure of Interests:</h3> <b>None declared.</b>