Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro
| Autor: | Gayane Manukyan, Jana Ulehlova, Eva Kriegova, Zuzana Mikulková, Anush Martirosyan, Sona Margaryan, Antonin Hlusi, Ludek Slavik, Tomas Papajik |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Neutrophils Immunology Anti-domain 1 β2GPI T cells NK cells 030204 cardiovascular system & hematology CD16 Peripheral blood mononuclear cell Epitope Monocytes 03 medical and health sciences 0302 clinical medicine Immune system Rheumatology Antigen Cytotoxic T cell Original Research B cells biology Chemistry Antiphospholipid antibodies Molecular biology 030104 developmental biology Plasma pool biology.protein Antibody CD8 Primary immune cells |
| Zdroj: | Autoimmunity Highlights |
| ISSN: | 2038-0305 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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