The annexin A5-mediated pathogenic mechanism in the antiphospholipid syndrome: Role in pregnancy losses and thrombosis Review uri icon

Overview

MeSH Major

  • Annexin A5
  • Antibodies, Antiphospholipid
  • Antiphospholipid Syndrome

abstract

  • Annexin A5 (AnxA5) binds to phospholipid bilayers, forming two-dimensional crystals that block the phospholipids from availability for coagulation enzyme reactions. Antiphospholipid (aPL) antibodies cause gaps in the ordered crystallization of AnxA5 which expose phospholipids and thereby accelerate blood coagulation reactions. The aPL antibody-mediated disruption of AnxA5 crystallization has been confirmed on artificial phospholipid bilayers and on cell membranes including endothelial cells, placental trophoblasts and platelets. Recently, we reported that hydroxychloroquine, a synthetic antimalarial drug, can reverse this antibody-mediated process through two mechanisms: (1) by inhibiting the formation of aPL IgG-beta2glycoprotein I complexes; and (2) by promoting the formation of a second layer of AnxA5 crystal 'patches' over areas where the immune complexes had disrupted AnxA5 crystallization. In another translational application, we have developed a mechanistic assay that reports resistance to AnxA5 anticoagulant activity in plasmas of patients with aPL antibodies. AnxA5 resistance may identify a subset of aPL syndrome patients for whom this is a mechanism for pregnancy losses and thrombosis. The elucidation of aPL-mediated mechanisms for thrombosis and pregnancy complications may open new paths towards addressing this disorder with targeted treatments and mechanistic assays.

publication date

  • April 2010

Research

keywords

  • Review

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1177/0961203310361485

PubMed ID

  • 20353989

Additional Document Info

start page

  • 460

end page

  • 9

volume

  • 19

number

  • 4