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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

  • Manukyan, Gayane1, 2
  • Martirosyan, Anush1
  • Slavik, Ludek2
  • Margaryan, Sona1, 2
  • Ulehlova, Jana2
  • Mikulkova, Zuzana2
  • Hlusi, Antonin2
  • Papajik, Tomas2
  • Kriegova, Eva2
  • 1 Institute of Molecular Biology NAS RA, 7 Hasratyan St., Yerevan, 0014, Armenia , Yerevan (Armenia)
  • 2 Palacky University Olomouc and Faculty Hospital, Olomouc, Czech Republic , Olomouc (Czechia)
Published Article
Autoimmunity Highlights
BioMed Central
Publication Date
Mar 02, 2020
DOI: 10.1186/s13317-020-00128-y
Springer Nature


Backgroundβ2-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.MethodsPeripheral 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.ResultsThe 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.ConclusionsTaking 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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