Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 110(02): 358-365
DOI: 10.1160/TH13-02-0149

Wound Healing and Inflammation/Infection

Schattauer GmbH

Antibodies against thrombin in dengue patients contain both anti-thrombotic and pro-fibrinolytic activities

Yung-Chun Chuang

¹Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan

²Center of Infectious Disease and Signaling Research, Medical College, National Cheng Kung University, Tainan, Taiwan

,

Yee-Shin Lin

²Center of Infectious Disease and Signaling Research, Medical College, National Cheng Kung University, Tainan, Taiwan

³Department of Microbiology and Immunology, Medical College, National Cheng Kung University, Tainan, Taiwan

,

Hsiao-Sheng Liu

²Center of Infectious Disease and Signaling Research, Medical College, National Cheng Kung University, Tainan, Taiwan

³Department of Microbiology and Immunology, Medical College, National Cheng Kung University, Tainan, Taiwan

,

Jen-Reng Wang

²Center of Infectious Disease and Signaling Research, Medical College, National Cheng Kung University, Tainan, Taiwan

⁴Department of Medical Laboratory Science and Biotechnology, Medical College, National Cheng Kung University, Tainan, Taiwan

,

Trai-Ming Yeh

²Center of Infectious Disease and Signaling Research, Medical College, National Cheng Kung University, Tainan, Taiwan

⁴Department of Medical Laboratory Science and Biotechnology, Medical College, National Cheng Kung University, Tainan, Taiwan

› Author Affiliations

Summary

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.

Keywords

Keywords

Coagulation factors - autoantibodies - haemostasis

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