You are here

Article Text

Article menu

Download PDFPDF

Scientific Abstracts
Publication Only
Scleroderma, myositis and related syndromes
AB0410 S100A4 PLASMA LEVELS CORRELATE WITH DISEASE ACTIVITY, SKIN FIBROSIS AND INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS PATIENTS
Free
  1. H. Štorkánová1,2,
  2. L. Andres Cerezo1,
  3. S. Oreska1,2,
  4. M. Špiritović1,3,
  5. B. Heřmánková1,3,
  6. M. Komarc4,
  7. K. Pavelka1,2,
  8. J. Vencovský1,2,
  9. J. H. W. Distler5,
  10. L. Šenolt1,2,
  11. R. Bečvář1,2,
  12. M. Tomcik1,2
  1. 1Institute of Rheumatology, -, Prague, Czech Republic
  2. 21st Faculty of Medicine, Charles University, Prague, Czech Republic, Department of Rheumatology, Prague, Czech Republic
  3. 3Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic, Department of Physiotherapy, Prague, Czech Republic
  4. 4Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic, Department of Methodology, Prague, Czech Republic
  5. 5University of Erlangen-Nuremberg, Erlangen, Germany, Department of Internal Medicine III and Institute for Clinical Immunology, Erlangen, Germany

Abstract

Background: In our previous study we demonstrated that S100A4 is overexpressed in scleroderma (SSc) skin, SSc fibroblasts and preclinical models of SSc in a TGF-β dependent manner. We showed that S100A4 is a new regulator of TGF-β signalling and its inhibition prevents the pro-fibrotic effects of TGF-β. Inactivation of S100A4 prevented dermal fibrosis induced by bleomycin and in Tsk-1 mice

Objectives: The aim of this study was to evaluate S100A4 in the peripheral blood of SSc patients and characterize its potential association with SSc-related features.

Methods: A total of 33 patients (29 females; mean age 52.8; disease duration 4.2 years; dcSSc/lcSSc = 8/25) who met the 2013 EULAR/ACR classification criteria for SSc and 20 healthy age- and sex-matched individuals were included in this study. Plasma levels of S100A4 were measured using ELISA (CUSABIO, Houston, USA). Data are presented as median (IQR).

Results: S100A4 plasma levels were significantly increased in SSc patients compared to healthy controls (78.6(32.3-146.5) vs. 43.4(32.3-53.4)ng/mL,p=0.011). Patients with diffuse cutaneous (dc)SSc had significantly higher levels of S100A4 than patients with limited cutaneous (lc)SSc or healthy controls (168.5(81.5-347.5) vs. 63.4(30.9-130.6),p=0.017,p=0.001, respectively). Plasma levels of S100A4 positively correlated with mRSS (r=0.556,p=0.001). Furthermore, S100A4 negatively correlated with forced vital capacity (FVC) and peripheral oxygen saturation (SpO2) (r=- 0.362,p=0.038;r=-0.414,p=0.029, respectively). S100A4 levels positively correlated with ESSG activity score (r=0.750,p<0.001). However, only correlations between S100A4 and mRSS, and ESSG activity score were approved at corrected level of statistical significance after Bonferroni’s correction (p<0.01). In a prospective analysis of patients (n=40) with progressive SSc-ILD treated with 6 (n=24) or 12 (n=16) monthly i.v. pulses of cyclophosphamide (CPA, 500 mg/m2), we observed a significant decrease in plasma S100A4 levels between the baseline samples (month 0) and blood drawn after 6 months of CPA treatment (76.3(52.9–98.6) vs. 73.2(44.4–98.6)ng/mL,p=0.013). Furthermore, baseline S100A4 levels predicted the change (m0-m6) in CRP and ESR levels after 6 months of CPA therapy (r=0.472,p=0.004;r=0.528,p=0.003, respectively).

Conclusion: We demonstrate that plasma S100A4 levels are significantly increased in SSc patients compared with healthy controls. Increased S100A4 is associated with the dcSSc subset, skin involvement, deteriorated parameters of interstitial lung disease and higher disease activity. In patients with progressive SSc-ILD, S100A4 declines after 6 months of cyclophosphamide therapy and predicts the systemic inflammatory response. These data further support our previous findings on the role of S100A4 as a regulator of TGF-β induced fibrosis in SSc.

Acknowledgements: Supported by MHCR023728, SVV–260373.

Disclosure of Interests: None declared

https://doi.org/10.1136/annrheumdis-2021-eular.462

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.