High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis
- Gisela Ruiz Heiland1,
- Heiner Appel2,
- Denis Poddubnyy2,
- Jochen Zwerina1,
- Axel Hueber1,
- Hildrun Haibel2,
- Xenofon Baraliakos3,
- Joachim Listing4,
- Martin Rudwaleit2,
- Georg Schett1,
- Joachim Sieper2,4
- 1Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen–Nuremberg, Erlangen, Germany
- 2Medical Department I, Rheumatology, Charité, Campus Benjamin Franklin, Berlin, Germany
- 3Rheumatism Centre, Region of Ruhr, Herne, Germany
- 4Department of Epidemiology, German Rheumatism Research Centre, Berlin, Germany
- Correspondence to Georg Schett, Department of Rheumatology, University of Erlangen–Nuremberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany;
- Received 21 October 2011
- Accepted 20 November 2011
- Published Online First 20 December 2011
Introduction The molecular mechanisms of syndesmophyte formation in ankylosing spondylitis (AS) are yet to be characterised. Molecules involved in bone formation such as Wnt proteins and their antagonists probably drive syndesmophyte formation in AS.
Methods This study investigated sequential serum levels of functional dickkopf-1 (Dkk1), a potent Wnt antagonist involved in bone formation in arthritis, by capture ELISA with its receptor LRP6 in 65 AS patients from the German Spondyloarthritis Inception Cohort. Dkk1 levels were then related to structural progression (syndesmophyte formation) as well as sclerostin and C-reactive protein (CRP) levels.
Results Functional Dkk1 levels were significantly (p=0.025) higher in patients with no syndesmophyte growth (6.78±5.48 pg/ml) compared with those with syndesmophyte growth (4.13±2.10 pg/ml). Dkk1 levels were highly correlated to serum sclerostin levels (r=0.71, 95% CI 0.53 to 0.82; p<0.001) but not to CRP (r=0.15, 95% CI −0.10 to 0.38; p=0.23).
Conclusion AS patients with no syndesmophyte formation show significantly higher functional Dkk1 levels suggesting that blunted Wnt signalling suppresses new bone formation and consequently syndesmophyte growth and spinal ankylosis. Similar to serum sclerostin levels, the functional Dkk1 level thus emerges as a potential biomarker for structural progression in patients with AS
Funding This study was supported by the Deutsche Forschungsgemeinschaft (SPP1468-IMMUNOBONE), the Bundesministerium für Bildung und Forschung (BMBF; projects ANCYLOSS and Competence Network Rheumatology), the MASTERSWITCH and BTCure projects of the European Union, the Interdisciplinary Centre for Clinical Research and the ELAN fund of the University of Erlangen-Nuremberg.
Competing interests None.
Ethics approval The GESPIC study was approved by the medical ethics committees of all participating centres.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.