Apras Sule, Ertenli Ihsan, Ozbalkan Zeynep, Kiraz Sedat, Ozturk M Akif, Haznedaroglu Ibrahim C, Cobankara Veli, Pay Salih, Calguneri Meral
Hacettepe University School of Medicine, Sehit Cetin Gorgu Street 17/3, 06570 Maltepe, Ankara, Turkey.
Arthritis Rheum. 2003 Aug;48(8):2256-61. doi: 10.1002/art.11081.
The endothelial damage of microvascular structures in systemic sclerosis (SSc; scleroderma) is associated with increased levels of endothelial adhesion molecules and endothelium-associated cytokines, including E-selectin and thrombomodulin. Although there is still no ideal specific pharmacologic therapy for SSc, cyclophosphamide has resulted in clinical improvement in patients with SSc-related active alveolitis. This study was designed to assess the expression of E-selectin and thrombomodulin in patients with early diffuse SSc, and to investigate the effects of oral cyclophosphamide combined with prednisolone therapy on the levels of these endothelium-associated cytokines and on the patients' clinical outcomes.
Thirteen patients with early diffuse SSc were treated with oral cyclophosphamide (2-2.5 mg/kg/day) and methylprednisolone (30 mg/every other day) for 1 year. The outcomes were determined as clinical (skin score) and laboratory parameters (including the erythrocyte sedimentation rate, complete blood cell count, levels of C-reactive protein, antinuclear antibody, anti-double-stranded DNA, rate of creatinine clearance, and findings on pulmonary function tests, esophageal manometry, and echocardiography). The concentrations of E-selectin and thrombomodulin were measured in the pretreatment and posttreatment serum samples from the SSc patients and from 12 healthy adults as controls.
In the patients with early diffuse SSc, pretreatment and posttreatment mean levels of E-selectin were 51 ng/ml (range 34.2-135.5) and 33.4 ng/ml (range 23-62.5), respectively (P = 0.01), and those of thrombomodulin were 82 ng/ml (range 35.8-120.5) and 74.6 ng/ml (range 23.3-91.3), respectively (P = 0.016). Clinical and laboratory parameters (the skin score and measures of pulmonary function [forced vital capacity and diffusing capacity for carbon monoxide]) were also improved (P < 0.05 for each) at the end of the followup period.
Combination therapy with cylophosphamide plus prednisolone is effective in the treatment of early diffuse SSc. Circulating levels of E-selectin and thrombomodulin not only demonstrate the extent of endothelial injury and/or activation, but also could be a useful marker to monitor the disease activity in SSc.
系统性硬化症（SSc；硬皮病）微血管结构的内皮损伤与内皮黏附分子及内皮相关细胞因子水平升高有关，包括E选择素和血栓调节蛋白。尽管目前仍没有针对SSc的理想特异性药物治疗方法，但环磷酰胺已使SSc相关活动性肺泡炎患者的临床症状得到改善。本研究旨在评估早期弥漫性SSc患者中E选择素和血栓调节蛋白的表达，并探讨口服环磷酰胺联合泼尼松龙治疗对这些内皮相关细胞因子水平及患者临床结局的影响。
13例早期弥漫性SSc患者接受口服环磷酰胺（2 - 2.5mg/kg/天）和甲泼尼龙（30mg/隔日）治疗1年。结局指标包括临床指标（皮肤评分）和实验室参数（包括红细胞沉降率、全血细胞计数、C反应蛋白水平、抗核抗体、抗双链DNA、肌酐清除率以及肺功能测试、食管测压和超声心动图检查结果）。在SSc患者及12名健康成年人作为对照的治疗前和治疗后血清样本中检测E选择素和血栓调节蛋白的浓度。
在早期弥漫性SSc患者中，治疗前和治疗后E选择素的平均水平分别为51ng/ml（范围34.2 - 135.5）和33.4ng/ml（范围23 - 62.5）（P = 0.01），血栓调节蛋白的平均水平分别为82ng/ml（范围35.8 - 120.5）和74.6ng/ml（范围23.3 - 91.3）（P = 0.016）。随访期末，临床和实验室参数（皮肤评分以及肺功能指标[用力肺活量和一氧化碳弥散量]）也得到改善（每项P < 0.05）。
环磷酰胺加泼尼松龙联合治疗对早期弥漫性SSc有效。E选择素和血栓调节蛋白的循环水平不仅可反映内皮损伤和/或活化程度，还可能是监测SSc疾病活动的有用标志物。
