Increased serum levels of fractalkine and mobilisation of CD34+CD45-endothelial progenitor cells in systemic sclerosis.
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.
Internal Medicine Department, Assistance Publique-Hôpitaux de Marseille (APHM), CHU Nord, 13015, Marseilles, France. audrey.benyamine@ap-hm.fr.|Haematology and Vascular Biology Laboratory, APHM, CHU Conception, 13005, Marseilles, France. audrey.benyamine@ap-hm.fr.|Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France. audrey.benyamine@ap-hm.fr.
Audrey
A
Benyamine
Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France.|Culture and Cell Therapy Laboratory, CICBT 1409, APHM, CHU Conception, 13005, Marseilles, France.
Jérémy
J
Magalon
Haematology and Vascular Biology Laboratory, APHM, CHU Conception, 13005, Marseilles, France.|Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France.
Sylvie
S
Cointe
Haematology and Vascular Biology Laboratory, APHM, CHU Conception, 13005, Marseilles, France.|Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France.
Romaric
R
Lacroix
Haematology and Vascular Biology Laboratory, APHM, CHU Conception, 13005, Marseilles, France.
Laurent
L
Arnaud
Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France.|Immunology Laboratory, APHM, CHU Conception, 13005, Marseilles, France.
Nathalie
N
Bardin
Internal Medicine Department, Assistance Publique-Hôpitaux de Marseille (APHM), CHU Nord, 13015, Marseilles, France.|Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France.
Pascal
P
Rossi
Internal Medicine Department, Assistance Publique-Hôpitaux de Marseille (APHM), CHU Nord, 13015, Marseilles, France.
Yves
Y
Francès
Internal Medicine Department, Assistance Publique-Hôpitaux de Marseille (APHM), CHU Nord, 13015, Marseilles, France.
Fanny
F
Bernard-Guervilly
Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France.|Internal Medicine Department, APHM, CHU Conception, 13005, Marseilles, France.
Gilles
G
Kaplanski
Internal Medicine Department, APHM, CHU Timone, 13005, Marseilles, France.
Jean-Robert
JR
Harlé
Internal Medicine Department, APHM, CHU Timone, 13005, Marseilles, France.
Pierre-Jean
PJ
Weiller
Dermatology Department, APHM, CHU Nord, 13015, Marseilles, France.
Philippe
P
Berbis
Centre d'Investigation Clinique Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques, APHM, CHU Timone, CHU Nord, Marseille, France.
David
D
Braunstein
Centre d'Investigation Clinique Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques, APHM, CHU Timone, CHU Nord, Marseille, France.
Elisabeth
E
Jouve
Centre d'Investigation Clinique Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques, APHM, CHU Timone, CHU Nord, Marseille, France.
Nathalie
N
Lesavre
Centre d'Investigation Clinique Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques, APHM, CHU Timone, CHU Nord, Marseille, France.
Françoise
F
Couranjou
Haematology and Vascular Biology Laboratory, APHM, CHU Conception, 13005, Marseilles, France.|Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France.
Françoise
F
Dignat-George
Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France.|Culture and Cell Therapy Laboratory, CICBT 1409, APHM, CHU Conception, 13005, Marseilles, France.
Florence
F
Sabatier
Haematology and Vascular Biology Laboratory, APHM, CHU Conception, 13005, Marseilles, France.|Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France.
Pascale
P
Paul
Internal Medicine Department, Assistance Publique-Hôpitaux de Marseille (APHM), CHU Nord, 13015, Marseilles, France.|Vascular Research Centre of Marseille (VRCM) UMR-S1076, INSERM, Aix-Marseille Université, 13385, Marseilles, Cedex, France.
Brigitte
B
Granel
D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002452:Cell Count; D002465:Cell Movement; D055252:Cell-Derived Microparticles / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000097:blood*; D066026:Endothelial Progenitor Cells / Q000378:metabolism* / Q000473:pathology; D019332:Endothelin-1 / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012595:Scleroderma, Systemic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D018952:Antigens, CD34; D015415:Biomarkers; D054428:Chemokine CX3CL1; D019332:Endothelin-1; D042461:Vascular Endothelial Growth Factor A; D017493:Leukocyte Common Antigens
Circulating endothelial cells; Endothelial homeostasis; Endothelial microparticles; Endothelial progenitor cells; Endothelin-1; Fractalkine; Systemic sclerosis; Vascular endothelial growth factor