title: Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression.
abstract: OBJECTIVE
  Antibody-mediated disruption of the annexin A5 anticoagulant shield has been posited to be a thrombogenic mechanism in the antiphospholipid syndrome. We recently showed that the antimalarial drug, hydroxychloroquine, dissociates antiphospholipid immune complexes and restores annexin A5 binding to planar phospholipid bilayer. Using quantitative immunoassays, we demonstrated similar effects on BeWo trophoblasts. We therefore, investigated the effects of the drug on localization of annexin A5 in primary cultures of human placental syncytiotrophoblasts.
  
  
  METHODS
  Laser confocal microscopy with computer-based morphometric analysis was used to localize annexin A5 and antiphospholipid antibodies on syncytiotrophoblasts exposed to polyclonal and monoclonal antiphospholipid and control immunoglobulin-Gs.
  
  
  RESULTS
  Hydroxychloroquine reversed the effects of the antiphospholipid antibodies on the syncytiotrophoblasts by markedly reducing immunoglobulin-G binding and restoring annexin A5 expression.
  
  
  CONCLUSIONS
  These results provide the first morphologic evidence for this effect of hydroxychloroquine on human placental syncytiotrophoblasts and support the possibility of novel treatments that target antiphospholipid antibody binding.
authors.affiliation: Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Xiao-Xuan
authors.initials: XX
authors.lastname: Wu
authors.forename: Seth
authors.initials: S
authors.lastname: Guller
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Rand
mesh_terms: D017304:Annexin A5 / Q000378:metabolism*; D017152:Antibodies, Antiphospholipid / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000187:drug effects / Q000276:immunology; D000962:Antimalarials / Q000494:pharmacology; D016736:Antiphospholipid Syndrome / Q000188:drug therapy / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D017304:Annexin A5; D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000962:Antimalarials; D007074:Immunoglobulin G; D006886:Hydroxychloroquine