Del Papa Nicoletta, Colombo Gualtiero, Fracchiolla Nicola, Moronetti Lorenza Mazzeo, Ingegnoli Francesca, Maglione Wanda, Comina Denise P, Vitali Claudio, Fantini Flavio, Cortelezzi Agostino
Department of Rheumatology, G. Pini Hospital, University of Milan, Milan, Italy.
Arthritis Rheum. 2004 Apr;50(4):1296-304. doi: 10.1002/art.20116.
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.
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.
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.
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.
循环内皮细胞（CECs）已在涉及血管损伤的不同情况下被描述。血管异常在系统性硬化症（SSc）的发病机制中起关键作用。本研究的目的是寻找SSc患者中CECs的存在情况，并评估其临床相关性及可能的致病作用。
研究队列包括46例SSc患者和40名健康对照者。使用FACScan进行五参数三色流式细胞术检测。CECs定义为CD45阴性、CD34阳性和P1H12阳性，活化的CECs定义为CD45阴性且P1H12阳性、CD62阳性或CD106阳性。祖细胞被鉴定为CD34阳性和CD133阳性。
与健康对照者相比，SSc患者的总CECs计数和活化CECs计数显著更高，且与疾病活动评分呈正相关。关于内脏受累情况，观察到CECs数量与肺动脉高压严重程度之间存在显著相关性。在SSc患者中观察到高水平的内皮祖细胞，且在疾病早期计数更高。
SSc患者中CECs的存在可能代表内皮疾病的直接证据，并且可能是活动性SSc一个有前景的新临床标志物。值得注意的是，仅在局限性皮肤型SSc患者中CECs与肺动脉高压和一氧化碳弥散能力受损之间的关联明显，这表明CECs在这个具有显著血管变化的疾病亚组中起重要作用。循环内皮祖细胞的检测可能代表早期SSc对血管缺血的一种反应，作为一种血管再生的尝试。
