Circulating endothelial progenitor cells in systemic sclerosis: association with disease severity
- J Avouac1,2,
- F Juin3,
- J Wipff1,2,
- P O Couraud4,
- G Chiocchia5,
- A Kahan1,
- C Boileau2,6,
- G Uzan3,
- Y Allanore1,2
- 1Paris Descartes University, Rheumatology A Department, Cochin Hospital, APHP, Paris, France
- 2INSERM U781, Necker Hospital, Paris, France
- 3INSERM U602, Paul Brousse Hospital, Villejuif, France
- 4Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France
- 5INSERM U567, Cochin Hospital, Paris, France
- 6UVSQ University, Biochemistry, Hormonology and Molecular Genetics Department, Ambroise Paré Hospital, AP-HP, Boulogne, France
- Dr Allanore Yannick, Hôpital Cochin, Service de Rhumatologie A, 27 rue du faubourg Saint Jacques, 75014 Paris, France;
- Accepted 20 December 2007
- Published Online First 3 January 2008
Background: Heterogeneous data have been reported regarding the detection and number of circulating endothelial progenitor cells (EPCs) in systemic sclerosis (SSc).
Objective: We investigated the number of circulating EPCs using recent recommendations and we quantified their late outgrowth in patients with SSc and healthy controls.
Patients and methods: EPCs, defined as Lin–/7AAD–/CD34+/CD133+/VEGFR-2+ cells, were quantified in 50 patients with SSc (mean age: 55 (16) years, disease duration: 9 (9) years) and 26 controls (mean age: 53 (19) years) by cell sorting/flow cytometry and by counting late outgrowth colony-forming units (CFU).
Results: Patients with SSc displayed higher circulating EPC counts than controls (median 86 (5–282) vs 49 (5–275)) EPCs for 1 million Lin– mononuclear cells; p = 0.01). Lower EPC counts were associated with the higher Medsger’s severity score (p = 0.01) and with the presence of past and/or current digital ulcers (p = 0.026). There was no difference for the number of late outgrowth EPC-CFUs between patients with SSc and controls in cell culture evaluation. The formation of colonies was associated with higher levels of circulating EPCs (p = 0.02) and the number of colonies correlated with levels of EPCs (R = 0.73, p = 0.0004), validating our combination of fluorescence-activated cell sorter surface markers.
Conclusions: We quantified circulating EPCs with an accurate combination of markers herein validated. Our data demonstrate increased circulating EPC levels in SSc, supporting their mobilisation from bone marrow. Furthermore, the subset of patients with digital vascular lesions and high severity score displayed low EPC counts, suggesting increased homing at this stage. The predictive value of this biomarker now warrants further evaluation.
Funding: Société Française de Rhumatologie, Institut SERVIER, Association des Sclérodermiques de France, Groupe Français de Recherche sur la Sclérodermie, Fondation pour la Recherche Médicale, Institut National de la Santé Et de la Recherche Médicale, Fond d’Etude et de Recherche du Corps Médical des Hôpitaux de Paris
Competing interests: None.