Kurzfassung

The anti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by an adaptive immune response against self phospholipid (PL)--binding proteins and clinically by recurrent thrombotic or thrombembolic events and/or fetal losses. Although APS is considered asan autoantibody-mediated disease, there is growing evidence that anti-phospholipid antibodies (aPL) are necessary but not sufficient for the clinical manifestations of the syndrome. In particular, mediators of the innate...The anti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by an adaptive immune response against self phospholipid (PL)--binding proteins and clinically by recurrent thrombotic or thrombembolic events and/or fetal losses. Although APS is considered as an autoantibody-mediated disease, there is growing evidence that anti-phospholipid antibodies (aPL) are necessary but not sufficient for the clinical manifestations of the syndrome. In particular, mediators of the innate immunity are increasingly recognized to be additionally involved in both the thrombogenic effects and fetal losses. In fact, complement activation and proinflammatory cytokines have been shown to be involved in fetal loss in an experimental model. Beyond this, a role for neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis have been demonstrated to play an additional role [1]. Finally, microbial infections have been reported to act as triggers for the production of autoantibodies cross-reacting with PL-binding proteins as well as inflammatory stimuli that potentiate the aPL thrombogenic effect. Altogether, these findings suggest a role for the innate immunity in APS pathogenesis. Toll-like receptors (TLR) directly recognize microbial structures and most of them are expressed in neutrophils. TLR triggering induces prompt inflammatory responses and mediates functional activation in immune effector cells. There is evidence that aPL, and in particular anti-beta(2) glycoprotein I antibodies, may activate endothelial cells and monocytes through TLR-4-dependent signalling. Whether or not TLR in conjuction with aPL may behave similarly in neutrophils is not known and is the focus of this project.
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