Bu C, Zhang C, Li Z, Gao L, Xie Z, Cai G
Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.
Clin Exp Immunol. 2007 Jul;149(1):31-9. doi: 10.1111/j.1365-2249.2007.03382.x. Epub 2007 Apr 11.
Reduced fibrinolytic activity has been described in primary anti-phospholipid syndrome (PAPS), and may be responsible for thrombotic events. Antibodies to tissue type plasminogen activator (t-PA) or plasminogen (PLG) might contribute to the hypofibrinolytic state in autoimmune diseases, but the clinical significance of these antibodies is still unclear in recurrent pregnancy loss (RPL). The aim of this study is to evaluate the prevalence and clinical significance of anti-PLG and anti-t-PA antibodies in 87 patients with a history of RPL: 54 women with well-defined PAPS (mean age 32.5 years; range 26-38) and 33 women with unexplained RPL (mean age 30 years; range 24-39). IgG anti-PLG antibodies were found in 20 and four patients from the group with RPL/PAPS and unexplained RPL, respectively; IgG anti-t-PA antibodies were found in 11 and two patients from the above two groups, respectively. IgG anti-PLG antibodies were associated with the high risk of RPL (OR 7.2, P = 0.004), especially with RPL/PAPS (OR 11.2, P < 0.001) evaluated by Fisher's exact test, while IgG anti-t-PA were associated with RPL/PAPS (OR 10.0, P = 0.01) but not with RPL (OR 6.8, P = 0.06). A significant inhibition of exogenous fibrinolysis was observed by IgG fractions from patients with anti-PLG or anti-t-PA antibodies on microplates and on the human umbilical vein endothelial cells, compared with those from healthy controls. The prevalence of IgG anti-PLG antibodies was high in RPL patients, especially in RPL/PAPS, while the prevalence of IgG anti-t-PA antibodies was high in RPL/PAPS but not in RPL, and some of them might inhibit fibrinolysis in patients.
原发性抗磷脂综合征（PAPS）中已发现纤维蛋白溶解活性降低，这可能是血栓形成事件的原因。针对组织型纤溶酶原激活物（t-PA）或纤溶酶原（PLG）的抗体可能导致自身免疫性疾病中的纤溶活性低下状态，但这些抗体在复发性流产（RPL）中的临床意义仍不明确。本研究的目的是评估87例有RPL病史患者中抗PLG和抗t-PA抗体的患病率及临床意义：54例明确诊断为PAPS的女性（平均年龄32.5岁；范围26 - 38岁）和33例不明原因RPL的女性（平均年龄30岁；范围24 - 39岁）。分别在RPL/PAPS组和不明原因RPL组中，20例和4例患者检测到IgG抗PLG抗体；上述两组中分别有11例和2例患者检测到IgG抗t-PA抗体。通过Fisher精确检验评估，IgG抗PLG抗体与RPL高风险相关（OR 7.2，P = 0.004），尤其是与RPL/PAPS相关（OR 11.2，P < 0.001），而IgG抗t-PA与RPL/PAPS相关（OR 10.0，P = 0.01）但与RPL无关（OR 6.8，P = 0.06）。与健康对照者相比，抗PLG或抗t-PA抗体患者的IgG组分在微孔板和人脐静脉内皮细胞上对外源性纤维蛋白溶解有显著抑制作用。RPL患者中IgG抗PLG抗体患病率较高，尤其是在RPL/PAPS中，而IgG抗t-PA抗体患病率在RPL/PAPS中较高但在RPL中不高，其中一些抗体可能抑制患者的纤维蛋白溶解。
