Circulating endothelial cells as a marker of ongoing vascular disease in systemic sclerosis
Nicoletta Del Papa1, Gualtiero Colombo, Nicola Fracchiolla
1Department of Rheumatology, G. Pini Hospital, University of Milan, Milan, Italy. delpapa@gpini.it
Insights
Circulating endothelial cells (CECs) are elevated in systemic sclerosis (SSc) patients, correlating with disease activity and pulmonary hypertension. These cells may indicate endothelial damage and serve as a marker for active SSc, especially in early stages.
Area of Science:
- Vascular Biology
- Rheumatology
- Immunology
Background:
- Vascular abnormalities are central to systemic sclerosis (SSc) pathogenesis.
- Circulating endothelial cells (CECs) are indicators of vascular injury.
- The role of CECs in SSc requires further investigation.
Purpose of the Study:
- To investigate the presence and clinical associations of CECs in SSc patients.
- To evaluate the potential pathogenic role of CECs in SSc.
- To explore CECs as a potential biomarker for SSc activity.
Main Methods:
- Flow cytometry was used to quantify CECs and activated CECs in 46 SSc patients and 40 healthy controls.
- CECs were identified as CD45-negative, CD34-positive, P1H12-positive cells.
- Endothelial progenitors were identified as CD34-positive, CD133-positive cells.
Main Results:
- SSc patients exhibited significantly higher total and activated CEC counts than controls.
- CEC levels correlated positively with SSc disease activity scores.
- Elevated endothelial progenitor counts were observed in SSc, particularly in early disease stages.
- CEC counts correlated with pulmonary hypertension severity in SSc patients.
Conclusions:
- Elevated CECs in SSc suggest endothelial disease and may serve as a biomarker for active SSc.
- CECs are associated with pulmonary hypertension and impaired carbon monoxide diffusing capacity in limited cutaneous SSc.
- Circulating endothelial progenitors may indicate vascular ischemia and revascularization attempts in early SSc.
Objective:
Circulating endothelial cells (CECs) have been described in different conditions involving vascular injury. Vascular abnormalities play a key role in the pathogenesis of systemic sclerosis (SSc). The aim of this study was to search for the presence of CECs in patients with SSc and to evaluate their clinical associations and possible pathogenic role.
Methods:
The study cohort included 46 patients with SSc and 40 healthy controls. Five-parameter, 3-color flow cytometry was performed with a FACScan. CECs were defined as CD45 negative, CD34 positive, and P1H12 positive, and activated CECs were defined as CD45 negative and P1H12 positive, CD62 positive, or CD106 positive. Progenitors were identified as CD34 positive and CD133 positive.
Results:
Total and activated CEC counts were significantly higher in SSc patients compared with healthy controls and were positively correlated with the disease activity score. With respect to visceral involvement, significant correlation was observed between the CEC number and the severity of pulmonary hypertension. High levels of endothelial progenitors were observed in patients with SSc, and the counts were higher in the early stages of disease.
Conclusion:
The presence of CECs in patients with SSc may represent direct evidence of endothelial disease and may be a promising new clinical marker for active SSc. Notably, the association between CECs and pulmonary hypertension and impaired carbon monoxide diffusing capacity was evident in patients with limited cutaneous SSc only, suggesting an important role for CECs in this disease subset with prominent vascular changes. Detection of circulating endothelial progenitors may represent a response to vascular ischemia in early SSc, as an attempt at revascularization.
