Boin Francesco, Franchini Stefano, Colantuoni Elizabeth, Rosen Antony, Wigley Fredrick M, Casciola-Rosen Livia
Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
Arthritis Rheum. 2009 Aug;60(8):2480-9. doi: 10.1002/art.24684.
Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti-beta2-glycoprotein I (anti-beta2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti-beta2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients.
Seventy-five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti-beta2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models.
Positivity for anti-beta2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P=0.017), with the IgA isotype of anti-beta2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti-beta2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5).
Anti-beta2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti-beta2GPI as a biomarker of vascular disease in SSc should be further explored.
系统性硬化症（SSc；硬皮病）的特征是独特的广泛血管受累，可导致严重的指端缺血、肺动脉高压（PAH）或其他器官功能障碍。微血栓形成事件和促凝血因子，如抗β2糖蛋白I（抗β2GPI）或抗心磷脂抗体（aCL），可能与这些表现的发生有关。本研究旨在调查抗β2GPI和aCL是否与SSc患者的大血管疾病相关，包括指端缺血性坏死和PAH。
对75例有指端缺血性坏死病史的SSc患者和75例匹配的SSc对照进行评估。检测抗着丝点抗体（ACAs）、抗β2GPI和aCL，并使用条件和简单逻辑回归模型确定临床相关性。
有指端缺血性坏死的SSc患者中抗β2GPI阳性率显著高于无指端缺血性坏死的患者（P=0.017），抗β2GPI的IgA亚型显示出最强的相关性（比值比[OR]4.0）。有指端缺血性坏死的患者与对照患者之间aCL频率无显著差异。在调整人口统计学特征、疾病类型、吸烟和ACAs后，抗β2GPI阳性与活动性指端缺血（OR 9.4）、超声心动图显示的PAH（OR 4.8）和死亡率（OR 2.9）显著相关。ACAs阳性与指端缺血性坏死病史相关（OR 3.28），但与PAH或死亡率无关。指端缺血性坏死病史与死亡率增加密切相关（OR 12.5）。
抗β2GPI与SSc中的大血管疾病显著相关，并独立预测死亡率。尚不清楚它是否具有致病作用，还是仅仅揭示了潜在的内皮损伤的存在。抗β2GPI作为SSc血管疾病生物标志物的应用应进一步探索。
