Abstract
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.
Highlights
Antiphospholipid antibodies is a heterogeneous family of autoantibodies directed primarily toward phospholipid binding proteins or single plasma proteins [1]
To address the main question of the study and to define cellular responses in response to Antiphospholipid antibodies (aPL), we developed an in vitro model which allowed analysing the influence of patient-derived aPL on the phenotype and activation status of monocytes, NK cells, T and B cells
The percentage and median fluorescence intensity (MFI) of CD142 were increased on monocytes treated with anti-domain 1 (D1)(+) compared to the cells cultured with anti-β2GPI domain 1 (anti-D1)(−) (P < 0.01 and P < 0.05, respectively) and seronegative (P < 0.001 and P < 0.001, respectively) plasma (Fig. 1)
Summary
Antiphospholipid antibodies (aPL) is a heterogeneous family of autoantibodies directed primarily toward phospholipid binding proteins or single plasma proteins [1]. Among a wide variety of known aPL, the clinical significance of anticardiolipin (aCL), anti-β2-glycoprotein I (anti-β2GPI) and lupus anticoagulant (LA) is well established [2]. Transient generation of aPL may be Manukyan et al Autoimmun Highlights (2020) 11:5 associated with various pathological conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren’s syndrome, infectious diseases, neurological or cardiac complications, and even in 1–5% of general healthy population [1]. The continuous presence of “classical” aPL, anti-β2GPI, aCL and LA, is a hallmark of the antiphospholipid syndrome (APS), that is the most common cause of acquired thrombophilia, associated with venous and/or arterial thrombosis and pregnancy complications [3]. Clinical, and experimental evidences suggested a positive association between aPL and thrombotic complications in APS patients [4]. LA and anti-β2GPI are commonly recognised as strong risk factors for thromboembolic events [5]
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