Insights into the pathophysiology of the antiphospholipid syndrome provided by atomic force microscopy

The antiphospholipid syndrome (APS) is an enigmatic autoimmune disorder in which patients present with thrombosis and/or recurrent pregnancy losses together with laboratory evidence for the presence of autoantibodies in the blood that recognize proteins that bind to anionic phospholipids - the most important of which is beta(2)-glycoprotein I(beta(2)GPI). Earlier, we hypothesized that the clinical manifestations arise from antibody-induced disruption of a two-dimensional anticoagulant crystal shield, composed of annexin A5, present on placental trophoblast plasma membranes. Accordingly, we reasoned that a high resolution imaging technology, such as atomic force microscopy could be used to investigate such molecular interactions at high resolution in a non-fixed hydrated environment. This review will focus on the contribution of this technique to the elucidation of the mechanism of APS. (C) 2012 Elsevier Ltd. All rights reserved.