Department of Medical Laboratory Science and Biotechnology, Medical College, National Cheng Kung University, Tainan, Taiwan.
Thromb Haemost. 2013 Aug;110(2):358-65. doi: 10.1160/TH13-02-0149. Epub 2013 Jun 6.
Dengue virus (DENV) infection may result in severe life-threatening Dengue haemorrhagic fever (DHF). The mechanisms causing haemorrhage in those with DHF are unclear. In this study, we demonstrated that antibodies against human thrombin were increased in the sera of Dengue patients but not in that of patients infected with other viruses. To further characterise the properties of these antibodies, affinity-purified anti-thrombin antibodies (ATAs) were collected from Dengue patient sera by thrombin and protein A/L affinity columns. Most of the ATAs belonged to the IgG class and recognized DENV nonstructural protein 1 (NS1). In addition, we found that dengue patient ATAs also cross-reacted with human plasminogen (Plg). Functional studies in vitro indicated that Dengue patient ATAs could inhibit thrombin activity and enhance Plg activation. Taken together, these results suggest that DENV NS1-induced thrombin and Plg cross-reactive antibodies may contribute to the development of haemorrhage in patients with DHF by interfering with coagulation and fibrinolysis.
登革热病毒（DENV）感染可能导致严重的危及生命的登革出血热（DHF）。导致 DHF 患者出血的机制尚不清楚。在这项研究中，我们证明了针对人凝血酶的抗体在登革热患者的血清中增加，但在感染其他病毒的患者的血清中没有增加。为了进一步描述这些抗体的特性，我们通过凝血酶和蛋白 A/L 亲和柱从登革热患者的血清中纯化了抗凝血酶抗体（ATAs）。大多数 ATAs 属于 IgG 类，可识别登革热非结构蛋白 1（NS1）。此外，我们发现登革热患者的 ATAs 也与人类纤溶酶原（Plg）发生交叉反应。体外功能研究表明，登革热患者的 ATAs 可以抑制凝血酶活性并增强 Plg 的激活。总之，这些结果表明，DENV NS1 诱导的凝血酶和 Plg 交叉反应性抗体可能通过干扰凝血和纤维蛋白溶解而导致 DHF 患者出血的发生。
