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Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis
  1. Jérôme Avouac1,2,
  2. Christophe Meune3,
  3. Barbara Ruiz2,
  4. Pierre Olivier Couraud2,
  5. Georges Uzan4,
  6. Catherine Boileau5,
  7. André Kahan1,
  8. Gilles Chiocchia2,6,
  9. Yannick Allanore1,2
  1. 1Rheumatology A department, Paris Descartes University, Cochin Hospital, APHP, Sorbonne Paris Cité, Paris, France
  2. 2INSERM U1016 and CNRS UMR8104, Paris Descartes University, Cochin Institute, Sorbonne Paris Cité, Paris, France
  3. 3Cardiology department, Paris Descartes University, Cochin Hospital, APHP, Sorbonne Paris Cité, Paris, France
  4. 4INSERM U972, Paul Brousse Hospital, Villejuif, France
  5. 5Hormonology and Molecular Genetics Department, Biochemistry Department, U.V.S.Q University, Ambroise Paré Hospital, APHP, Boulogne, France
  6. 6Rheumatology Department, Ambroise Paré Hospital, U.V.S.Q University, APHP, Boulogne, France
  1. Correspondence to Professor Yannick Allanore, Hôpital Cochin, Service de rhumatologie A, 27 rue du Faubourg Saint Jacques, 75014 Paris, France; yannick.allanore{at}


Objective To evaluate the possible merit of endothelial markers for the prediction of ischaemic digital ulcers in patients with systemic sclerosis (SSc).

Methods Circulating endothelial progenitor cells (EPC), circulating endothelial cells and serum levels of placental growth factor (PlGF), soluble vascular adhesion molecule and vascular endothelial growth factor were measured in a prospective cohort of 100 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up.

Results After the follow-up period, 17 patients developed new digital ulcers. By multivariate analysis focused on biomarkers, high PlGF serum levels and low EPC counts were identified as predictors of the occurrence of at least one new digital ulcer. In a secondary model including biomarkers together with clinical SSc characteristics all predictors of digital ulcers defined by p≤0.1 in univariate analysis, high PlGF serum levels (HR 7.26, 95% CI 1.92 to 27.41) and a history of digital ulcers (HR 9.32, 95% CI 1.51 to 59.83) were identified as independent predictors of a new digital ulcer. In an alternative model excluding patients with a history of digital ulcers at baseline, high PlGF serum levels (HR 13.46, 95% CI 1.58 to 114.73) and low EPC counts (HR 7.95, 95% CI 2.09 to 30.09) remained predictive of new digital ulcer occurrence during follow-up.

Conclusion This study identified high PlGF serum levels and low circulating EPC counts as predictors of new digital ulcers in SSc. It highlights the critical role of angiogenesis in this vascular outcome. These markers may improve digital ulcer risk stratification and therefore allow earlier therapeutic intervention.

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  • Funding This study received financial support from the Société Française de Rhumatologie, Association des Sclérodermiques de France, Groupe Français de Recherche sur la Sclérodermie (bourse AMPLI), INSERM, Agence Nationale pour la Recherche (grant no R07094KS) and Fond d'Etude et de Recherche du Corps Médical des Hôpitaux de Paris. It was also supported by an investigator-initiated research grant from Pfizer Ltd.

  • Competing interests None.

  • Ethics approval Ethics approval was received from CPP Ile de France 3.

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

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