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

Yung Chun Chuang, Yee Shin Lin, Hsiao Sheng Liu, Jen Reng Wang, Trai Ming Yeh

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)358-365
Number of pages8
JournalThrombosis and Haemostasis
Volume110
Issue number2
DOIs
Publication statusPublished - 2013 Aug 2

Fingerprint

Dengue
Thrombin
Antibodies
Severe Dengue
Dengue Virus
Anti-Idiotypic Antibodies
Plasminogen
Hemorrhage
Antibody Affinity
Staphylococcal Protein A
Fibrinolysis
Virus Diseases
Blood Proteins
Proteins
Immunoglobulin G
Viruses
Serum

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

@article{e192ee08e7d54e5996aaa4ae925c50c3,
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.",
author = "Chuang, {Yung Chun} and Lin, {Yee Shin} and Liu, {Hsiao Sheng} and Wang, {Jen Reng} and Yeh, {Trai Ming}",
year = "2013",
month = "8",
day = "2",
doi = "10.1160/TH13-02-0149",
language = "English",
volume = "110",
pages = "358--365",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "2",

}

Antibodies against thrombin in dengue patients contain both anti-thrombotic and pro-fibrinolytic activities. / Chuang, Yung Chun; Lin, Yee Shin; Liu, Hsiao Sheng; Wang, Jen Reng; Yeh, Trai Ming.

In: Thrombosis and Haemostasis, Vol. 110, No. 2, 02.08.2013, p. 358-365.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antibodies against thrombin in dengue patients contain both anti-thrombotic and pro-fibrinolytic activities

AU - Chuang, Yung Chun

AU - Lin, Yee Shin

AU - Liu, Hsiao Sheng

AU - Wang, Jen Reng

AU - Yeh, Trai Ming

PY - 2013/8/2

Y1 - 2013/8/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84879892110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879892110&partnerID=8YFLogxK

U2 - 10.1160/TH13-02-0149

DO - 10.1160/TH13-02-0149

M3 - Article

C2 - 23740201

AN - SCOPUS:84879892110

VL - 110

SP - 358

EP - 365

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 2

ER -