Bäck Jennie, Lood Christian, Bengtsson Anders A, Ekdahl Kristina Nilsson, Nilsson Bo
Arthritis Res Ther. 2013;15(6):R206. doi: 10.1186/ar4399.
Patients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE.
Fibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38) previous VD and from matched healthy controls (n = 68) were analyzed for the presence of complexes formed between contact system enzymes and antithrombin (AT) or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory parameters.
Fibrin clots elicited FXII activation and acted as co-factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa-C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa-AT was elevated in the SLE patients with a history of VD, while the corresponding levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated strongly with platelet parameters. The odds ratio for VD among the SLE patients was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa-C1INH and increased levels of FXIIa-AT.
Activation of FXII is elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered levels of FXIIa-serpin complexes, supporting that the contact system is involved in this disease. FXIIa-serpin complexes are strongly associated with previous VD in SLE patients, suggesting that these complexes are potential biomarkers for monitoring and assessing the risk of thrombotic events in SLE.
系统性红斑狼疮（SLE）患者存在持续的血小板活化，血栓形成事件风险增加，而传统心血管危险因素无法解释这一现象。因子（F）XII在血栓形成中可能起重要作用，且由活化血小板触发。因此，我们探讨接触系统是否参与SLE的炎症和血管疾病（VD）。
将纤维蛋白凝块与纯化的FXII或全血孵育，研究FXII的活化和调节。分析有（n = 31）或无（n = 38）既往VD的SLE患者以及匹配的健康对照（n = 68）的血浆中接触系统酶与抗凝血酶（AT）或C1抑制剂（C1INH）形成的复合物的存在情况，并结合临床数据和实验室参数进行评估。
纤维蛋白凝块引发FXII活化，并作为AT的辅助因子。在凝血血浆中，FXIIa-AT水平升高，FXIIa-C1INH水平降低。SLE患者中也存在类似的相互关系。有VD病史的SLE患者中FXIIa-AT升高，而相应的FXIIa-C1INH水平显著降低。FXIIa-AT与血小板参数密切相关。SLE患者中，FXIIa-C1INH水平低时VD的比值比为8.9，FXIIa-AT水平高时为6.1，而FXIIa-C1INH水平降低且FXIIa-AT水平升高时则增至23.4。
体外和体内血栓形成反应过程中，纤维蛋白可引发FXII活化，且纤维蛋白作为类肝素辅助因子发挥作用并调节AT。SLE患者中FXIIa-丝氨酸蛋白酶抑制剂复合物水平发生改变，支持接触系统参与了该疾病。FXIIa-丝氨酸蛋白酶抑制剂复合物与SLE患者既往VD密切相关，提示这些复合物是监测和评估SLE患者血栓形成事件风险的潜在生物标志物。
