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Induction of tissue factor expression by anti-β2-glycoprotein I is mediated by tumor necrosis factor α

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Abstract

Antiphospholipid antibodies (aPL) are heterogeneous and there is evidence that binding specificity determines which cellular effects they can trigger. We have therefore hypothesised that the induction of tissue factor (TF) in monocytes and endothelial cells by aPL depends on their binding specificity. To further investigate this, we have analyzed the ability of three human monoclonal aPL with distinctly different binding specificities to induce transcription and cell surface expression of TF in monocytes and endothelial cells. Results with human monoclonal aPL were validated with IgG-fractions obtained from patients with APS. We confirmed previous results that a lipid reactive human monoclonal aPL rapidly induced TF transcription and cell surface expression in monocytes and endothelial cells. A monoclonal aPL reactive against β2 glycoprotein I (β2GPI) induced TF with a delayed time course. This was fully dependent on the induction of tumor necrosis factor alpha (TNFα) secretion as capture of TNFα by adalimumab prevented TF induction. This pattern was confirmed with patient IgG fractions. Both lipid reactive and anti-β2GPI induced TF transcription. Unexpectedly, this activity of anti-β2GPI was mediated fully by TNFα which was secreted in response to incubation with anti-β2GPI. The role of TNFα in mediating TF induction by anti-β2GPI may have wider implications for APS pathogenesis.

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Acknowledgements

This study was supported by the German Federal Ministry of Education and Research (BMBF 01EO1003). The authors are responsible for the contents of this publication.

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Authors and Affiliations

  1. Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Langenbeckstr. 1, 55131, Mainz, Germany

    Anne Hollerbach, Nadine Müller-Calleja, Antje Canisius, Carolin Orning & Karl J. Lackner

  2. Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany

    Anne Hollerbach & Nadine Müller-Calleja

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  1. Anne Hollerbach
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  2. Nadine Müller-Calleja
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  3. Antje Canisius
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  4. Carolin Orning
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  5. Karl J. Lackner
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Contributions

AH and NM-C designed the study, performed experiments and reviewed data, wrote the manuscript; AC and CO performed experiments; KJL designed the study, reviewed data, wrote the manuscript.

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Correspondence to Karl J. Lackner.

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Hollerbach, A., Müller-Calleja, N., Canisius, A. et al. Induction of tissue factor expression by anti-β2-glycoprotein I is mediated by tumor necrosis factor α. J Thromb Thrombolysis 49, 228–234 (2020). https://doi.org/10.1007/s11239-019-01970-2

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