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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2017

Open Access 01-12-2017 | Research article

Increased serum levels of fractalkine and mobilisation of CD34+CD45− endothelial progenitor cells in systemic sclerosis

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

Published in: Arthritis Research & Therapy | Issue 1/2017

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
Appendix
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Metadata
Title
Increased serum levels of fractalkine and mobilisation of CD34+CD45− endothelial progenitor cells in systemic sclerosis
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
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2017
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-017-1271-7

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