Pathogenesis of the antiphospholipid syndrome: an additional example of the mosaic of autoimmunity.

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by an adaptive immune response against self-PL-binding proteins ending in the production of specific autoantibodies. Antiphospholipid antibodies (aPL; and in particular anti-beta2 glycoprotein I antibodies) are formal diagnostic markers and pathogenic antibodies. Although APS may be considered as an autoantibody-mediated disease, there is now evidence that aPL are necessary but not sufficient to trigger some of the clinical manifestations of the syndrome. For example, additional factors, such as mediators of the innate immunity are now recognized to play a key role as second hits able to induce the thrombotic events in the presence of the autoantibodies. The APS scenario is also supplemented by the influence of genetically determined factors. Finally, environmental agents - in particular infectious ones - were 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 do support the concept of a mosaic of factors that participate to the pathogenesis of the syndrome at different levels.