Some antiphospholipid antibodies bind to various serine proteases in hemostasis and tip the balance toward hypercoagulant states

Chen, PP; Wu, Mei‐Fang; Hahn, BH

doi:10.1177/0961203310361488

Cited by 8 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we found that monoclonal antibodies generated from DENV-immunised mice can cross-react with human Plg and enhance its activation (12). It is known that plasmin (Plm) and thrombin share homologous trypsin/thrombin-like serine protease domains (13) and that some mAbs generated from patients with antiphospholipid syndrome (APS) can bind various serine proteases including Plg and thrombin and tip the balance toward a hypercoagulant state (13)(14)(15)(16)(17). Therefore, we hypothesised that some anti-Dengue antibodies may bind to thrombin and inhibit its activity to thus promote haemorrhage in patients infected with DENV.…”

Section: Introductionmentioning

confidence: 99%

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

Chuang¹,

Lin²,

Liu³

et al. 2013

Thromb Haemost

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Chuang¹,

Lin²,

Liu³

et al. 2013

Thromb Haemost

View full text Add to dashboard Cite

show abstract

“…10 Antiphospholipid antibodies were shown to interact with endothelial cells, monocytes and platelets converting them into a prothrombotic state and to inhibit several natural anticoagulants like activated protein C, prothrombin/thrombin and plasmin. 11,12 Pregnancy itself can act as a second hit, therefore it is possible that, during gestation, multiple thrombotic events can damage placental blood flow and impair the placental development. In fact, multiple placental infarcts have been described in pregnancies complicated with aPL.…”

Section: The First Year Of Lifementioning

confidence: 99%

“…Thus, we could assume that the pathogenesis of perinatal thrombosis associated with aPL can be explained by both the transplacental passage of maternal antibodies and the possible de novo synthesis of IgM and IgG aPL in the fetus and newborn. 7–39…”

Section: Neonatal Thrombosis and Antiphospholipid Antibodiesmentioning

confidence: 99%

“APS pregnancy – The offspring”

Bitsadze

Nalli

Khizroeva

et al. 2020

Lupus

View full text Add to dashboard Cite

Background Antiphospholipid antibody syndrome (APS) is an autoimmune disease that affects women in childbearing age. In recent years, great improvements were achieved in the management of pregnancies in these women. Prematurity could be an issue in these pregnancies, mainly due to the direct pathogenic effect of antiphospholipid antibodies (aPL) on the placental surface. Maternal IgG aPL can cross the placenta and theoretically interact with the growing fetus; it could reach the fetal brain because of the incompleteness of the fetal blood-brain barrier: whether this can have an effect on brain development is still debated. Neonatal thrombosis episodes have been described in children positive for aPL, not always associated with maternal antibody positivity, suggesting the hypothesis of a possible aPL de novo synthesis in fetus and neonates. Methods A keyword-based literature search was conducted. We also described a case of neonatal catastrophic antiphospholipid syndrome (CAPS). Results Offspring of patients with APS are generally healthy but the occurrence of neonatal thrombosis or minor neurological disorders were reported. Conclusions The limited number of the available data on this sensitive issue supports the need for further studies. Clinical follow-up of children of mothers with APS seems to be important to exclude, in the neonatal period, the occurrence of aPL associated pathological events such as thrombosis, and in the long-term, impairment in learning skills or behavioral problems.

show abstract

“…These antibodies bind to phospholipids and protein epitopes found in cardiolipin, annexin V, prothrombin and β-2 glycoprotein-1 [24]. The antiphospholipid antibodies that recognize epitopes on β-2 glycoprotein-1 also bind serine proteases involved in hemostasis and fibrinolysis and hence promote thrombosis [79].…”

Section: Hypercoagulabilitymentioning

confidence: 99%

“…Tissue factor pathway inhibitor activity is reduced in SLE and this is associated with increased levels of tissue factor and subsequent hypercoagulability [82]. Antiphospholipid antibodies bind to components of the coagulation cascade and activate the coagulation system leading to a procoagulant state along with decreased fibrinolysis via reducing activity of tPA [79][80][81].…”

Section: Hypercoagulabilitymentioning

confidence: 99%

Thrombophilia in Systemic Lupus Erythematosus: A Review of Multiple Mechanisms and Resultant Clinical Outcomes

Dhar¹,

Sokol²

2013

Pregnancy Thrombophilia - The Unsuspected Risk

View full text Add to dashboard Cite

cardiovascular disease and clotting, the multiple mechanisms for hypercoagulability in SLE, and discuss the complexity of this problem in this population.Pregnancy Thrombophilia -The Unsuspected Risk Premature cardiovascular diseaseLupus-specific thrombophilic factors contribute to premature cardiac disease and atherosclerosis in this population. These lupus specific factors can affect the endothelium resulting in premature arterial vascular disease contributing to the accelerated/premature atherosclerosis observed in SLE [24]. Atheroma formation is initiated when oxidized low density lipoprotein (LDL) is taken up by foam cells in vascular endothelium [24][25]. High density lipoprotein (HDL) and Apo-A1 are protective factors against atherosclerosis. β-2 glycoprotein-1 binding to oxidized LDL facilitates uptake by foam cells [26]. Patients with SLE have antibodies to LDL/ β-2 glycoprotein-1 complexes, HDL, and Apo -A1 [26][27]. Antibodies to HDL and Apo A-1 cross react with cardiolipin and prevent HDL and Apo-1 protection against atherosclerosis. Antibodies to oxidized LDL may cross react with β-2 glycoprotein-1 and may enhance uptake, thus promoting plaque formation [25][26][27][28]. Anticardiolipin antibody binding exposes immunogenic and normally hidden (or cryptic) epitopes on β-2 glycoprotein-1, which can bind to anti-β-2 glycoprotein-1 antibodies. These antibodies bind to adhered β-2 glycoprotein-1 on endothelial cells which causes endothelial activation and subsequent up regulation of inflammatory and procoagulant factors [24][25][26]. In addition, adhered β-2 glycoprotein-1 on oxidized LDL promotes LDL uptake by macrophages, thus facilitating plaque formation [24][25][26]28]. During the acute phase response, HDL can be converted to pro-inflammatory molecules which promote LDL oxidation. Chronic inflammation can cause HDL dysfunction in SLE. HDL has been found to be pro-inflammatory in women with SLE and is termed pro-inflammatory HDL or piHDL [25][26]28]. More than 85% patients with SLE and carotid plaques had piHDL vs. 40% in those without plaques [27]. Pro-inflammatory HDL is an independent risk factor for atherosclerosis in rheumatoid arthritis and antiphospholipid antibody syndrome [26,28]. The prevalence of moderate to severe atherosclerosis in SLE at autopsy is 52% [29]. There is a higher prevalence of coronary artery disease in SLE than general population which is not predicted by traditional risk factors or increase in lupus activity alone [30][31][32][33][34][35][36][37][38][39]. Mortality studies show coronary artery disease (CAD) /myocardial infarction (MI) is a frequent cause of death in SLE and occurs in 11-48% of SLE patients [3,[30][31][32][33][34][35]. Death from CAD in SLE is disproportionately larger in late disease, with CAD/MI being the leading cause of death in SLE survivors. This accounts for the late peak in mortality in SLE [36][37][38]. Although there are a greater number of CAD risk factors (hypertension, diabetes mellitus, dyslipidemia, sedentary life style) in SLE patients than ...

show abstract

Some antiphospholipid antibodies bind to various serine proteases in hemostasis and tip the balance toward hypercoagulant states

Cited by 8 publications

References 21 publications

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

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

“APS pregnancy – The offspring”

Thrombophilia in Systemic Lupus Erythematosus: A Review of Multiple Mechanisms and Resultant Clinical Outcomes

Contact Info

Product

Resources

About