循环内皮细胞损伤标记物与抗中性粒细胞胞质抗体相关血管炎活动性的联系

Significance of circulating endothelial biomarkers in patients with ANCA associated vasculitis

目的:探讨外周血液中内皮细胞损伤标记物循环内皮细胞(CECs)数量、可溶性血栓调节蛋白(sTM)、血浆血管性假血友病因子(vWF)、E选择素(ES)和血管细胞黏附分子1(VCAM-1)水平与抗中性粒细胞胞质抗体(ANCA)相关血管炎(AAV)活动性的联系。方法:84例AAV患者,根据伯明翰评分(BVAS)评估血管炎活动性将其分为活动组(n=56,男性23例,女性33例,平均年龄48.1±16.8岁,BVAS评分13.6±2.4分)和缓解组(n=28,男性9例,女性19例,平均年龄50.2±16.4岁,BVAS评分0分)。性别、年龄相匹配健康志愿者20例为对照组。免疫磁珠分离方法检测CECs数量,ELISA法检测血浆sTM、vWF、ES和VCAM-1水平,并分别比较三组上述指标的差异。结果:活动组CECs、sTM、vWF和ES水平均显著高于健康对照组(P<0.01)。缓解组血CECs、sTM、vWF和ES与健康对照组比较无显著差异,活动组和缓解组血浆VCAM-1水平与健康对照组比较均无显著差异。与缓解组比较,活动组CECs[(30±12)个/mlvs(17±5)个/ml,P<0.01]与sTM[(9.5±6.8)ng/mlvs(6.1±3.4)ng/ml,P<0.01]水平显著升高,但经血清肌酐(SCr)校正后,两组间sTM水平无显著差异。两组间血浆vWF和ES也无显著差异(P>0.05)。活动组sTM水平与SCr和尿蛋白水平呈正相关性,CECs、vWF、ES和VCAM-1水平与SCr和尿蛋白无相关性。结论:循环内皮细胞数量与血管炎活动性密切相关,可作为临床判断ANCA相关血管炎活动性的重要指标。

Objective： To detect various endothelial markers of circulating endothelial e, ells（ CECs ）, soluble thrombomodulin（sTM） , von Willebrand factor （ vWF）, E-selectin and Vascular cell adhesion molecule 1 （ VCAM-1 ） in patients with active and remission stage of ANCA associated vasculitis,and to explore the relationship between endothelial markers and the activity of ANCA associated vasulitis （AAV）. Methodology：Fifty six patients with AAV in active phase [ M ：23, F ：33, mean age （48. 1 ± 16. 8 ） y, BVAS score （ 13.6 ± 2. 4 ） ], 28 patients in remission phase [ M ： 9, F ： 19, mean age （50. 2 ± 16. 4）y,BVAS score 0] ,and 20 healthy controls were enrolled in this study. The CECs were isolated from peripheral blood by use of Dynabeads coated with antibodies againsl CD146, and the plasma sTM, vWF, E-selectin and ignificance of VCAM-1 were detected with ELISA. Results： CECs, vWF, E-selectin and sTM levels, but not VCAM-I, were higher in the active phase of AAV than tha in controls （ P 〈 0. 01 ） , no signKicant differences of endothelial markers were found between AAV patients in remission and controls. The CECs [ （30 ± 1 ） eells/ml vs （ 17 ± 5.0） eells/ml, P 〈 0. 01 ] and levels of plasma sTM [ （9.5 ± 6. 8）ng/ml vs （6.1 ±3.4） ng/ml,P 〈 0. 01 ] were significant increased in active AAV patients than that in remission, whereas corrected tor renal function, sTM （lid not significam, and plasma vWF and E-selectin levels showed no significant difl＇erences between patients in active phase and in remission patients. The sTM level in the active phase was positive related with serum creatinine and urine protein,while elevated sTM levels were associated with higher serum creatinine levels. The endothelial markers had no relation with crescents and fibrinoid necrotic lesion.Conclusion：Circulating endothelial cells is potential biomarker in evaluating the activity of ANCA associated vasulitis.