Université de Paris, INSERM UMR_S1148, Paris Cedex, France.
Laboratoire d'Hématologie, AP-HP, Hôpital Bichat, Paris Cedex, France.
Thromb Haemost. 2020 May;120(5):758-767. doi: 10.1055/s-0040-1709526. Epub 2020 May 5.
Ligneous conjunctivitis (LC) is a rare disorder associated with plasminogen deficiency characterized by chronic fibrin deposits in the eyelids. All patients with plasminogen deficiency do not develop LC, whose underlying mechanisms remain unknown.
We investigated whether fibrinolytic activity was correlated with phenotype and/or genotype in patients suffering from LC and their relatives.
Plasminogen activity/antigen levels and mutations were determined in 10 patients with LC, 17 of their asymptomatic relatives, and 10 healthy individuals used as a control group. Plasma fibrinolytic activity was evaluated using three different assays: (1) tissue-plasminogen activator (t-PA) front lysis, (2) cell-based urokinase-dependent euglobulin clot lysis (ECLT) at the surface of corneal cells, and (3) urokinase-dependent plasminogen activation.
Plasminogen activity varied from <10 to 40% in patients, 36 to 105% in relatives, and >80% in control healthy individuals. Homozygous K19E mutation was associated with normal antigenic plasminogen levels. In front-lysis experiments, all patients had a lower fibrinolysis rate as compared with their relatives and to control individuals. The cell-based ECLT and plasminogen activation assay demonstrated that urokinase-mediated fibrinolysis was not impaired in patients with homozygous K19E mutation compared with the other mutants.
We confirm that plasminogen levels fail to predict LC occurrence. In these conditions, t-PA clot lysis front is useful to predict clinical outcome in plasminogen deficiency. Moreover, we provide evidence that occurrence of LC overlaps quantitative and qualitative plasminogen deficiencies. The homozygous K19E mutation is associated with isolated impaired t-PA-mediated fibrinolysis compared with other mutants.
黏膜性结膜炎（LC）是一种罕见的疾病，与纤溶酶原缺乏有关，其特征是眼睑中有慢性纤维蛋白沉积。并非所有纤溶酶原缺乏的患者都会发生 LC，其潜在机制尚不清楚。
我们研究了患有 LC 的患者及其亲属的纤溶活性是否与表型和/或基因型相关。
在 10 例 LC 患者、17 例无症状亲属和 10 例健康对照者中测定纤溶酶原活性/抗原水平和突变。使用三种不同的测定方法评估血浆纤维蛋白溶解活性：（1）组织型纤溶酶原激活物（t-PA）前纤维蛋白溶解；（2）角膜细胞表面依赖细胞的尿激酶依赖性优球蛋白纤维蛋白溶解（ECLT）；（3）尿激酶依赖性纤溶酶原激活。
患者的纤溶酶原活性从<10%到 40%不等，亲属的活性从 36%到 105%不等，健康对照者的活性>80%。K19E 纯合突变与正常抗原性纤溶酶原水平相关。在前纤维蛋白溶解实验中，所有患者的纤溶率均低于其亲属和健康对照者。基于细胞的 ECLT 和纤溶酶原激活测定表明，与其他突变体相比，纯合 K19E 突变患者的尿激酶介导的纤溶作用并未受损。
我们证实纤溶酶原水平不能预测 LC 的发生。在这些情况下，t-PA 凝块溶解前沿可用于预测纤溶酶原缺乏症的临床结局。此外，我们提供的证据表明，LC 的发生与定量和定性的纤溶酶原缺乏重叠。与其他突变体相比，K19E 纯合突变与 t-PA 介导的纤溶作用受损有关。
