Independent association of anti-beta(2)-glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients.
Independent association of anti-beta(2)-glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients.
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DOI：
10.1002/art.24684
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发表时间：
2009-08
影响因子：
--
通讯作者：
Casciola-Rosen, Livia
中科院分区：
文献类型：
--
作者：
Boin, Francesco;Franchini, Stefano;Colantuoni, Elizabeth;Rosen, Antony;Wigley, Fredrick M.;Casciola-Rosen, Livia
硬皮病（SSc）的特征是一种独特的广泛性血管疾病，可导致严重的手指缺血、肺动脉高压（PAH）或其他器官功能障碍。微血栓事件和促凝因子，如抗β 2糖蛋白1（B2GPI）或抗心磷脂（aCL）抗体可能与这些表现的发生有关。本研究调查了抗B2GPI和aCL抗体是否与SSc患者中的大血管疾病（包括缺血性手指缺失和PAH）相关。对75例有缺血性手指缺失病史的SSc患者和75例匹配的SSc对照进行了评价。抗着丝粒（ACA），抗B2GPI和ACL抗体进行了测试，并使用条件和简单的逻辑回归模型测量临床关联。抗B2GPI，而不是ACL，在手指缺失患者中显著更常见（p=0.01），伊加同种型显示出最强的相关性（OR 4.0）。在调整人口统计学、疾病类型、吸烟和ACA后，抗B2GPI与活动性手指缺血（OR 9.4）、PAH的超声心动图证据（OR 4.8）和死亡率（OR 2.9）显著相关。ACA阳性与手指缺失史相关（OR 3.8），但与PAH或死亡率无关。手指缺失史与死亡率增加密切相关（OR 12.5）。抗B2 GPI抗体与SSc大血管疾病显着相关，并独立预测死亡率。目前尚不清楚它们是否发挥致病作用或仅仅揭示潜在的内皮损伤的存在。抗B2GPI抗体作为SSc血管疾病的生物标志物的应用应进一步探讨。
Scleroderma (SSc) is characterized by a unique widespread vascular disease that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH) or other organ dysfunction. Microthrombotic events and pro-coagulable factors such as anti-beta 2 glycoprotein 1 (B2GPI) or anti-cardiolipin (aCL) antibodies may be implicated in the development of these manifestations. This study investigated whether anti-B2GPI and aCL antibodies are correlated with macrovascular disease including ischemic digital loss and PAH in SSc patients. 75 SSc patients with history of ischemic digital loss and 75 matched SSc controls were evaluated. Anti-centromere (ACA), anti-B2GPI and aCL antibodies were tested and clinical associations measured using conditional and simple logistic regression models. Anti-B2GPI, but not aCL, were significantly more frequent (p=0.01) in digital loss patients, with IgA isotype showing the strongest association (OR 4.0). After adjusting for demographics, disease type, smoking and ACA, anti-B2GPI were significantly associated with active digital ischemia (OR 9.4), echocardiographic evidence for PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.8), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5). Anti-B2GPI antibodies are significantly associated with macrovascular disease in SSc and independently predict mortality. It is unclear whether they play a pathogenic role or simply reveal the presence of underlying endothelial injury. The use of anti-B2GPI antibodies as a biomarker of vascular disease in SSc should be further explored.
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