title: Antibodies against thrombin in dengue patients contain both anti-thrombotic and pro-fibrinolytic activities.
abstract: 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.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Medical College, National Cheng Kung University, Tainan, Taiwan. today@mail.ncku.edu.tw
authors.forename: Yung-Chun
authors.initials: YC
authors.lastname: Chuang
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
authors.forename: Hsiao-Sheng
authors.initials: HS
authors.lastname: Liu
authors.forename: Jen-Reng
authors.initials: JR
authors.lastname: Wang
authors.forename: Trai-Ming
authors.initials: TM
authors.lastname: Yeh
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral; D001323:Autoantibodies / Q000097:blood*; D001777:Blood Coagulation / Q000276:immunology; D003429:Cross Reactions; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D005342:Fibrinolysis / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D010958:Plasminogen / Q000276:immunology; D011516:Prothrombin / Q000276:immunology; D019595:Severe Dengue / Q000097:blood* / Q000209:etiology / Q000276:immunology*; D013917:Thrombin / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D001323:Autoantibodies; D007074:Immunoglobulin G; C079340:NS1 protein, Dengue virus type 2; D017361:Viral Nonstructural Proteins; D011516:Prothrombin; D010958:Plasminogen; D013917:Thrombin