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Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro

BACKGROUND: β2-Glycoprotein I (β2GPI) represents the major antigenic target for antiphospholipid antibodies (aPL), with domain 1 (D1) being identified as a risk factor for thrombosis and pregnancy complications in APS. We aimed to analyse the ability of aPL, and particularly anti-D1 β2GPI, to stimul...

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Autores principales: Manukyan, Gayane, Martirosyan, Anush, Slavik, Ludek, Margaryan, Sona, Ulehlova, Jana, Mikulkova, Zuzana, Hlusi, Antonin, Papajik, Tomas, Kriegova, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065342/
https://www.ncbi.nlm.nih.gov/pubmed/32127041
http://dx.doi.org/10.1186/s13317-020-00128-y
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author Manukyan, Gayane
Martirosyan, Anush
Slavik, Ludek
Margaryan, Sona
Ulehlova, Jana
Mikulkova, Zuzana
Hlusi, Antonin
Papajik, Tomas
Kriegova, Eva
author_facet Manukyan, Gayane
Martirosyan, Anush
Slavik, Ludek
Margaryan, Sona
Ulehlova, Jana
Mikulkova, Zuzana
Hlusi, Antonin
Papajik, Tomas
Kriegova, Eva
author_sort Manukyan, Gayane
collection PubMed
description BACKGROUND: β2-Glycoprotein I (β2GPI) represents the major antigenic target for antiphospholipid antibodies (aPL), with domain 1 (D1) being identified as a risk factor for thrombosis and pregnancy complications in APS. We aimed to analyse the ability of aPL, and particularly anti-D1 β2GPI, to stimulate prothrombotic and proinflammatory activity of immune cells in vitro. METHODS: Peripheral blood mononuclear cells (PBMCs) from 11 healthy individuals were incubated with: (1) “anti-D1(+)”—pooled plasma derived from patients suspected of having APS contained anticardiolipin antibodies (aCL), lupus anticoagulant (LA), anti-β2GPI and anti-D1 β2GPI; (2) “anti-D1(−)”—pooled plasma from patients suspected of having APS contained aCL, LA, anti-β2GPI, and negative for anti-D1 β2GPI; (3) “seronegative”—negative for aPL. RESULTS: The presence of anti-D1(+) and anti-D1(−) plasma resulted in increased HLA-DR and CD11b on monocytes. While only anti-D1(+) plasma markedly increased the percentage and median fluorescence intensity (MFI) of CD142 (tissue factor, TF) on monocytes in comparison with those cultured with anti-D1(−) and seronegative plasma. Anti-D1(+) plasma resulted in increased percentage and MFI of activation marker CD69 on NK and T cytotoxic cells. Expression of IgG receptor FcγRIII(CD16) on monocytes and NK cells was down-regulated by the anti-D1(+) plasma. CONCLUSIONS: Taking together, our study shows the ability of patient-derived aPL to induce immune cell activation and TF expression on monocytes. For the first time, we demonstrated the influence of anti-D1 β2GPI on the activation status of monocytes, NK and cytotoxic T cells. Our findings further support a crucial role of D1 epitope in the promotion of thrombosis and obstetrical complications in APS.
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spelling pubmed-70653422020-03-16 Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro Manukyan, Gayane Martirosyan, Anush Slavik, Ludek Margaryan, Sona Ulehlova, Jana Mikulkova, Zuzana Hlusi, Antonin Papajik, Tomas Kriegova, Eva Auto Immun Highlights Original Research BACKGROUND: β2-Glycoprotein I (β2GPI) represents the major antigenic target for antiphospholipid antibodies (aPL), with domain 1 (D1) being identified as a risk factor for thrombosis and pregnancy complications in APS. We aimed to analyse the ability of aPL, and particularly anti-D1 β2GPI, to stimulate prothrombotic and proinflammatory activity of immune cells in vitro. METHODS: Peripheral blood mononuclear cells (PBMCs) from 11 healthy individuals were incubated with: (1) “anti-D1(+)”—pooled plasma derived from patients suspected of having APS contained anticardiolipin antibodies (aCL), lupus anticoagulant (LA), anti-β2GPI and anti-D1 β2GPI; (2) “anti-D1(−)”—pooled plasma from patients suspected of having APS contained aCL, LA, anti-β2GPI, and negative for anti-D1 β2GPI; (3) “seronegative”—negative for aPL. RESULTS: The presence of anti-D1(+) and anti-D1(−) plasma resulted in increased HLA-DR and CD11b on monocytes. While only anti-D1(+) plasma markedly increased the percentage and median fluorescence intensity (MFI) of CD142 (tissue factor, TF) on monocytes in comparison with those cultured with anti-D1(−) and seronegative plasma. Anti-D1(+) plasma resulted in increased percentage and MFI of activation marker CD69 on NK and T cytotoxic cells. Expression of IgG receptor FcγRIII(CD16) on monocytes and NK cells was down-regulated by the anti-D1(+) plasma. CONCLUSIONS: Taking together, our study shows the ability of patient-derived aPL to induce immune cell activation and TF expression on monocytes. For the first time, we demonstrated the influence of anti-D1 β2GPI on the activation status of monocytes, NK and cytotoxic T cells. Our findings further support a crucial role of D1 epitope in the promotion of thrombosis and obstetrical complications in APS. BioMed Central 2020-03-02 /pmc/articles/PMC7065342/ /pubmed/32127041 http://dx.doi.org/10.1186/s13317-020-00128-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Research
Manukyan, Gayane
Martirosyan, Anush
Slavik, Ludek
Margaryan, Sona
Ulehlova, Jana
Mikulkova, Zuzana
Hlusi, Antonin
Papajik, Tomas
Kriegova, Eva
Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro
title Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro
title_full Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro
title_fullStr Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro
title_full_unstemmed Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro
title_short Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro
title_sort anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate nk cells and cd8+ cells in vitro
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065342/
https://www.ncbi.nlm.nih.gov/pubmed/32127041
http://dx.doi.org/10.1186/s13317-020-00128-y
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