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Anti-β2-glycoprotein I autoantibodies influence thrombin generation parameters via various mechanisms

Permanent link
https://hdl.handle.net/10037/24683
DOI
https://doi.org/10.1016/j.thromres.2020.10.032
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Accepted manuscript version (PDF)
Date
2020-11-06
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Szabó, Gábor; Debreceni, Ildikó Beke; Tarr, Tünde; Soltesz, P.; Østerud, Bjarne; Kappelmayer, János
Abstract
Introduction

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by recurrent thrombotic events, pregnancy loss and thrombocytopenia and the presence of antiphospholipid antibodies (APL). The exact pathomechanism of APS is still unknown, thus we investigated the effect of anti-β2-glycoprotein I (anti-β2GPI) on thrombin generation in different plasma samples.

Methods - For the separation of anti-β2GPI IgG, overall 12 APS patients were selected. The criteria were the existence of lupus anticoagulant, and the presence of anti-CL and anti-β2GPI, the latter exceeding at least 25 times the upper reference limit. We purified anti-β2GPI IgG antibodies from APS patients by affinity chromatography and added the antibodies to normal pooled, and heterozygous forms of inherited thrombophilia plasma samples (prothrombin G20210A, factor V Leiden). To further specify the mechanism of the effect, we also used factor deficient plasmas in the thrombin generation assay.

Results - In normal pooled plasma, the anti-β2GPI significantly prolonged Lag Time according to the lupus anticoagulant effect, in contrast, it also elevated Peak Thrombin significantly, which suggests a procoagulant effect. The antibody was also able to exert this multi-faceted effect both in FVLeiden heterozygous plasma and prothrombin G20210A heterozygous polymorphism, however, the prolonging effect was more remarkable in the latter. By using factor deficient plasmas, it was found that FVII is required for the prolongation, while intrinsic factors are needed for the elevation of the Peak Thrombin.

Conclusion - The anti-β>2GPI autoantibodies exert their effect in both normal and thrombophilic plasmas via various mechanisms.

Description
Accepted manuscript version, licensed CC BY-NC-ND 4.0.
Publisher
Elsevier
Citation
Szabó, Debreceni, Tarr, Soltesz, Østerud, Kappelmayer. Anti-β2-glycoprotein I autoantibodies influence thrombin generation parameters via various mechanisms. Thrombosis Research. 2021;197:124-131
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  • Artikler, rapporter og annet (medisinsk biologi) [1105]
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