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Elevated serum levels of sonic hedgehog are associated with fibrotic and vascular manifestations in systemic sclerosis
  1. Christian Beyer1,
  2. Dörte Huscher2,
  3. Andreas Ramming1,
  4. Christina Bergmann1,
  5. Jerome Avouac3,
  6. Serena Guiducci4,
  7. Florian Meier5,
  8. Serena Vettori6,
  9. Elise Siegert7,
  10. Veronika K Jaeger8,
  11. Britta Maurer9,
  12. Gabriela Riemekasten10,
  13. Ulrich Walker8,
  14. Ulf Müller-Ladner5,
  15. Gabriele Valentini6,
  16. Marco Matucci-Cerinic4,
  17. Yannick Allanore3,
  18. Oliver Distler9,
  19. Georg Schett1,
  20. Jörg H W Distler1
  1. 1 Department of Internal Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany
  2. 2 Epidemiology Unit, German Rheumatism Research Centre Berlin, A Leibniz Institute, Berlin, Germany
  3. 3 Service de Rhumatologie A, Hôpital Cochin, INSERM 1016, Paris, France
  4. 4 Division of Medicine & Rheumatology, University of Florence, Florence, Italy
  5. 5 Department of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Kerckhoff Clinic, Bad Nauheim, Germany
  6. 6 Department of Internal and Experimental Medicine, Rheumatology Unit, Second University of Naples, II Policlinico, Naples, Italy
  7. 7 Department Rheumatology and Clinical Immunology, Charité University Hospital Berlin, Berlin, Germany
  8. 8 Department of Rheumatology, University Hospital Basel, Basel, Switzerland
  9. 9 Department of Rheumaklinik, University Zurich, Zurich, Switzerland
  10. 10 Clinic for Rheumatology, University of Lübeck, Lübeck, Germany
  1. Correspondence to Jörg H W Distler, Department of Internal Medicine III, University Erlangen-Nuremberg, D-91054, Erlangen, Germany; joerg.distler{at}

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Fibrotic tissue remodelling and vascular alterations cause high morbidity and mortality in patients with systemic sclerosis (SSc).1 2 While the pathogenesis of SSc is only partially understood, recent evidence demonstrates a fundamental role of hedgehog signalling in fibrotic disease manifestations. Hedgehog signalling is activated in fibrotic SSc skin, and it induces an SSc-like phenotype in resting fibroblasts.3 Overexpression of sonic hedgehog (SHH) induces skin fibrosis, whereas inhibition of hedgehog signalling ameliorates experimental fibrosis.4

Based on these experimental findings, this European Scleroderma Trials and Research group (EUSTAR) multicentre cooperative study investigates whether circulating SHH may serve as a surrogate marker for a more severe disease phenotype in patients with SSc. We decided to evaluate SHH serum levels rather than total circulating SHH. Measurements of SHH serum levels are easy and robust but may not assess particulated SHH in various different extracellular vesicles. …

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  • Contributors CB and JHWD performed and evaluated experiments and wrote the manuscript. All other authors provided samples and clinical data and commented on the manuscript.

  • Competing interests None declared.

  • Ethics approval Approved by the following universities: Erlangen, Zurich, Basel, Paris, Florence, Giessen, Naples.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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