Interpreting high levels of unfolded Von Willebrand Factor in patients with the antiphospholipid syndrome

IntroductionUnfolded Von Willebrand Factor (VWF) is increased in thrombotic pathologies such as myocardial infarction. Unfolded VWF mediates the binding of platelets without the need for collagen. β2-glycoprotein I (β2-GPI) is a natural inhibitor of the platelet-VWF interaction. The antiphospholipid...

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Main Authors: Romy de Laat-Kremers, Shengshi Huang, Hugo ten Cate, Marisa Ninivaggi, Bas de Laat, Katrien Devreese
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1514433/full
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author Romy de Laat-Kremers
Shengshi Huang
Shengshi Huang
Hugo ten Cate
Hugo ten Cate
Marisa Ninivaggi
Bas de Laat
Bas de Laat
Katrien Devreese
Katrien Devreese
author_facet Romy de Laat-Kremers
Shengshi Huang
Shengshi Huang
Hugo ten Cate
Hugo ten Cate
Marisa Ninivaggi
Bas de Laat
Bas de Laat
Katrien Devreese
Katrien Devreese
author_sort Romy de Laat-Kremers
collection DOAJ
description IntroductionUnfolded Von Willebrand Factor (VWF) is increased in thrombotic pathologies such as myocardial infarction. Unfolded VWF mediates the binding of platelets without the need for collagen. β2-glycoprotein I (β2-GPI) is a natural inhibitor of the platelet-VWF interaction. The antiphospholipid syndrome (APS) is associated with thrombosis, with an important pathophysiological role of auto-antibodies directed against β2-GPI.Methods(Unfolded) VWF levels were studied in normal controls (n=93), APS patients (n=64), non-APS thrombosis patients (n=39) and non-APS auto-immune disease (AID) patients (n=49.ResultsUnfolded VWF levels were respectively, 53%, 50% and 36% higher in APS patients, non-APS thrombosis patients and AID patients, compared to normal controls (p<0.0001). Unfolded VWF levels above the 90th percentile in normal controls were associated with an odds of APS (OR: 8.51; CI:3.26 - 22.2; p<0.001), compared to ORs of non-APS thrombosis (OR:5.87; CI:2.07 - 16.7, p=0.001) and AID (OR:3.71; CI:1.40 – 9.87; p=0.009). DiscussionWe found that APS patients have high levels of unfolded VWF in their circulation. In APS, auto-antibodies against-β2-GPI may interfere with the β2-GPI-mediated inhibition of VWF-platelet interaction. Therefore, the higher unfolded VWF levels in APS could in part explain the association of APS and thrombotic complications.
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spelling doaj-art-6758ae5ee5bd4224b27a5e08ee1d3ee72025-08-20T02:50:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15144331514433Interpreting high levels of unfolded Von Willebrand Factor in patients with the antiphospholipid syndromeRomy de Laat-Kremers0Shengshi Huang1Shengshi Huang2Hugo ten Cate3Hugo ten Cate4Marisa Ninivaggi5Bas de Laat6Bas de Laat7Katrien Devreese8Katrien Devreese9Department of Data Analysis and Artificial Intelligence, Synapse Research Institute, Maastricht, NetherlandsDepartment of Functional Coagulation, Synapse Research Institute, Maastricht, NetherlandsDepartment of Internal Medicine and Biochemistry, Maastricht University Medical Center, Maastricht, NetherlandsDepartment of Internal Medicine and Biochemistry, Maastricht University Medical Center, Maastricht, NetherlandsCardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, NetherlandsDepartment of Functional Coagulation, Synapse Research Institute, Maastricht, NetherlandsDepartment of Data Analysis and Artificial Intelligence, Synapse Research Institute, Maastricht, NetherlandsDepartment of Functional Coagulation, Synapse Research Institute, Maastricht, NetherlandsCoagulation Laboratory, Department of Laboratory Medicine, Ghent University Hospital, Ghent, BelgiumDepartment of Diagnostic Sciences, Ghent University, Ghent, BelgiumIntroductionUnfolded Von Willebrand Factor (VWF) is increased in thrombotic pathologies such as myocardial infarction. Unfolded VWF mediates the binding of platelets without the need for collagen. β2-glycoprotein I (β2-GPI) is a natural inhibitor of the platelet-VWF interaction. The antiphospholipid syndrome (APS) is associated with thrombosis, with an important pathophysiological role of auto-antibodies directed against β2-GPI.Methods(Unfolded) VWF levels were studied in normal controls (n=93), APS patients (n=64), non-APS thrombosis patients (n=39) and non-APS auto-immune disease (AID) patients (n=49.ResultsUnfolded VWF levels were respectively, 53%, 50% and 36% higher in APS patients, non-APS thrombosis patients and AID patients, compared to normal controls (p<0.0001). Unfolded VWF levels above the 90th percentile in normal controls were associated with an odds of APS (OR: 8.51; CI:3.26 - 22.2; p<0.001), compared to ORs of non-APS thrombosis (OR:5.87; CI:2.07 - 16.7, p=0.001) and AID (OR:3.71; CI:1.40 – 9.87; p=0.009). DiscussionWe found that APS patients have high levels of unfolded VWF in their circulation. In APS, auto-antibodies against-β2-GPI may interfere with the β2-GPI-mediated inhibition of VWF-platelet interaction. Therefore, the higher unfolded VWF levels in APS could in part explain the association of APS and thrombotic complications.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1514433/fullVon Willbrand Factorantiphospholipid syndromethrombosisunfolded VWFVWF pro-peptide
spellingShingle Romy de Laat-Kremers
Shengshi Huang
Shengshi Huang
Hugo ten Cate
Hugo ten Cate
Marisa Ninivaggi
Bas de Laat
Bas de Laat
Katrien Devreese
Katrien Devreese
Interpreting high levels of unfolded Von Willebrand Factor in patients with the antiphospholipid syndrome
Frontiers in Immunology
Von Willbrand Factor
antiphospholipid syndrome
thrombosis
unfolded VWF
VWF pro-peptide
title Interpreting high levels of unfolded Von Willebrand Factor in patients with the antiphospholipid syndrome
title_full Interpreting high levels of unfolded Von Willebrand Factor in patients with the antiphospholipid syndrome
title_fullStr Interpreting high levels of unfolded Von Willebrand Factor in patients with the antiphospholipid syndrome
title_full_unstemmed Interpreting high levels of unfolded Von Willebrand Factor in patients with the antiphospholipid syndrome
title_short Interpreting high levels of unfolded Von Willebrand Factor in patients with the antiphospholipid syndrome
title_sort interpreting high levels of unfolded von willebrand factor in patients with the antiphospholipid syndrome
topic Von Willbrand Factor
antiphospholipid syndrome
thrombosis
unfolded VWF
VWF pro-peptide
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1514433/full
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