Abstract：
Systemic vasculitis is a heterogenous group of autoimmune diseases characterized by enhanced cardiovascular mortality. Endothelial dysfunction is associated with accelerated vascular damage, representing a core pathophysiologic mechanism contributing to excess CV risk. Recent studies have also shown that complement activation holds significant role in the pathogenesis of Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) -associated vasculitis (AAV). Given the potential crosstalk between the endothelium and complement, we aimed to assess, for the first time simultaneously, easily accessible biomarkers of endothelial dysfunction and complement activation in SV.
We measured circulating endothelial microvesicles (EMVs) and soluble complement components representative of alternative, classical and terminal activation (C5b-9, C1q, Bb fragments, respectively) in a meticulously selected group of patients with systemic vasculitis, but without cardiovascular disease. Individuals free from systemic diseases, who were matched with patients for cardiovascular risk factors(hypertension, diabetes, smoking, dyslipidemia), comprised the control group.
We studied 60 individuals (30 in each group). Patients with systemic vasculitis had elevated EMVs, higher levels of C5b-9 [536.4(463.4) vs 1200.94457.3), p = 0.003] and C1q [136.2(146.5 vs 204.2(232.9), p = 0.0129], compared to controls [232.0 (243.5) vs 139.3(52.1), p < 0.001]. In multivariate analysis both EMVs and C5b-9 were independently associated with disease duration (p = 0.005 and p = 0.004 respectively), yet not with disease activity.
Patients with systemic vasculitis exhibit impaired endothelial function and complement activation, both assessed by easily accessible biomarkers, even in the absence of cardiovascular disease manifestations. EMVs and soluble complement components such as C5b-9 and C1q could be used as early biomarkers of endothelial dysfunction and complement activation, respectively, in clinical practice during the course of SV, yet their predictive value in terms of future cardiovascular disease warrants further verification in appropriately designed studies.
We measured circulating endothelial microvesicles (EMVs) and soluble complement components representative of alternative, classical and terminal activation (C5b-9, C1q, Bb fragments, respectively) in a meticulously selected group of patients with systemic vasculitis, but without cardiovascular disease. Individuals free from systemic diseases, who were matched with patients for cardiovascular risk factors(hypertension, diabetes, smoking, dyslipidemia), comprised the control group.
We studied 60 individuals (30 in each group). Patients with systemic vasculitis had elevated EMVs, higher levels of C5b-9 [536.4(463.4) vs 1200.94457.3), p = 0.003] and C1q [136.2(146.5 vs 204.2(232.9), p = 0.0129], compared to controls [232.0 (243.5) vs 139.3(52.1), p < 0.001]. In multivariate analysis both EMVs and C5b-9 were independently associated with disease duration (p = 0.005 and p = 0.004 respectively), yet not with disease activity.
Patients with systemic vasculitis exhibit impaired endothelial function and complement activation, both assessed by easily accessible biomarkers, even in the absence of cardiovascular disease manifestations. EMVs and soluble complement components such as C5b-9 and C1q could be used as early biomarkers of endothelial dysfunction and complement activation, respectively, in clinical practice during the course of SV, yet their predictive value in terms of future cardiovascular disease warrants further verification in appropriately designed studies.
摘要：
目的：系统性血管炎是一组异质性的自身免疫性疾病，其特征是心血管死亡率增加。内皮功能障碍与加速的血管损伤有关，代表导致心血管风险过度的核心病理生理机制。最近的研究还表明，补体激活在抗中性粒细胞胞浆自身抗体（ANCA）相关血管炎（AAV）的发病机理中起着重要作用。鉴于内皮和补体之间的潜在串扰，我们旨在评估，第一次同时，在SV中容易获得的内皮功能障碍和补体激活的生物标志物。
方法：我们测量了循环内皮微泡（EMVs）和可溶性补体成分，经典和终末激活(C5b-9，C1q，Bb碎片,分别)在精心挑选的一组系统性血管炎患者中，但没有心血管疾病.没有全身性疾病的个体，与心血管危险因素患者相匹配(高血压，糖尿病,吸烟,血脂异常)，组成对照组。
结果：我们研究了60个个体（每组30个）。全身性血管炎患者的EMV升高，更高水平的C5b-9[536.4（463.4）vs1200.94457.3），p=0.003]和C1q[136.2（146.5对204.2（232.9），p=0.0129],与对照组[232.0（243.5）vs139.3（52.1）相比，p<0.001]。在多变量分析中，EMV和C5b-9与疾病持续时间独立相关（分别为p=0.005和p=0.004）。但没有疾病活动。
结论：系统性血管炎患者表现为内皮功能和补体激活受损，两者都通过容易获得的生物标志物进行评估，即使没有心血管疾病的表现。EMV和可溶性补体成分如C5b-9和C1q可用作内皮功能障碍和补体激活的早期生物标志物。分别,在临床实践中，在SV的过程中，然而,它们对未来心血管疾病的预测价值值得在适当设计的研究中进一步验证.
方法：我们测量了循环内皮微泡（EMVs）和可溶性补体成分，经典和终末激活(C5b-9，C1q，Bb碎片,分别)在精心挑选的一组系统性血管炎患者中，但没有心血管疾病.没有全身性疾病的个体，与心血管危险因素患者相匹配(高血压，糖尿病,吸烟,血脂异常)，组成对照组。
结果：我们研究了60个个体（每组30个）。全身性血管炎患者的EMV升高，更高水平的C5b-9[536.4（463.4）vs1200.94457.3），p=0.003]和C1q[136.2（146.5对204.2（232.9），p=0.0129],与对照组[232.0（243.5）vs139.3（52.1）相比，p<0.001]。在多变量分析中，EMV和C5b-9与疾病持续时间独立相关（分别为p=0.005和p=0.004）。但没有疾病活动。
结论：系统性血管炎患者表现为内皮功能和补体激活受损，两者都通过容易获得的生物标志物进行评估，即使没有心血管疾病的表现。EMV和可溶性补体成分如C5b-9和C1q可用作内皮功能障碍和补体激活的早期生物标志物。分别,在临床实践中，在SV的过程中，然而,它们对未来心血管疾病的预测价值值得在适当设计的研究中进一步验证.
