Title |
Increased serum levels of fractalkine and mobilisation of CD34+CD45− endothelial progenitor cells in systemic sclerosis
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Published in |
Arthritis Research & Therapy, March 2017
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DOI | 10.1186/s13075-017-1271-7 |
Pubmed ID | |
Authors |
Audrey Benyamine, Jérémy Magalon, Sylvie Cointe, Romaric Lacroix, Laurent Arnaud, Nathalie Bardin, Pascal Rossi, Yves Francès, Fanny Bernard-Guervilly, Gilles Kaplanski, Jean-Robert Harlé, Pierre-Jean Weiller, Philippe Berbis, David Braunstein, Elisabeth Jouve, Nathalie Lesavre, Françoise Couranjou, Françoise Dignat-George, Florence Sabatier, Pascale Paul, Brigitte Granel |
Abstract |
The disruption of endothelial homeostasis is a major determinant in the pathogenesis of systemic sclerosis (SSc) and is reflected by soluble and cellular markers of activation, injury and repair. We aimed to provide a combined assessment of endothelial markers to delineate specific profiles associated with SSc disease and its severity. We conducted an observational, single-centre study comprising 45 patients with SSc and 41 healthy control subjects. Flow cytometry was used to quantify circulating endothelial microparticles (EMPs) and CD34(+) progenitor cell subsets. Colony-forming unit-endothelial cells (CFU-ECs) were counted by culture assay. Circulating endothelial cells were enumerated using anti-CD146-based immunomagnetic separation. Blood levels of endothelin-1, vascular endothelial growth factor (VEGF) and soluble fractalkine (s-Fractalkine) were evaluated by enzyme-linked immunosorbent assay. Disease-associated markers were identified using univariate, correlation and multivariate analyses. Enhanced numbers of EMPs, CFU-ECs and non-haematopoietic CD34(+)CD45(-) endothelial progenitor cells (EPCs) were observed in patients with SSc. Patients with SSc also displayed higher serum levels of VEGF, endothelin-1 and s-Fractalkine. s-Fractalkine levels positively correlated with CD34(+)CD45(-) EPC numbers. EMPs, s-Fractalkine and endothelin-1 were independent factors associated with SSc. Patients with high CD34(+)CD45(-) EPC numbers had lower forced vital capacity values. Elevated s-Fractalkine levels were associated with disease severity, a higher frequency of pulmonary fibrosis and altered carbon monoxide diffusion. This study identifies the mobilisation of CD34(+)CD45(-) EPCs and high levels of s-Fractalkine as specific features of SSc-associated vascular activation and disease severity. This signature may provide novel insights linking endothelial inflammation and defective repair processes in the pathogenesis of SSc. |
X Demographics
Geographical breakdown
Country | Count | As % |
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France | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 41 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 7 | 17% |
Researcher | 6 | 15% |
Student > Postgraduate | 4 | 10% |
Lecturer | 3 | 7% |
Other | 3 | 7% |
Other | 5 | 12% |
Unknown | 13 | 32% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 12 | 29% |
Immunology and Microbiology | 4 | 10% |
Agricultural and Biological Sciences | 3 | 7% |
Nursing and Health Professions | 2 | 5% |
Biochemistry, Genetics and Molecular Biology | 2 | 5% |
Other | 4 | 10% |
Unknown | 14 | 34% |