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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1687-1695. Prepublished online as a Blood First Edition Paper on June 24, 2008; DOI 10.1182/blood-2008-03-144204. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-03-144204v1 112/5/1687    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rand, J. H. Articles by Taatjes, D. J. Search for Related Content PubMed PubMed Citation Articles by Rand, J. H. Articles by Taatjes, D. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Hydroxychloroquine directly reduces the binding of antiphospholipid antibody–β2-glycoprotein I complexes to phospholipid bilayers Jacob H. Rand1, Xiao-Xuan Wu1, Anthony S. Quinn2, Pojen P. Chen3, James J. Hathcock4, and Douglas J. Taatjes2 1 Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; 2 Department of Pathology and Microscopy Imaging Center, College of Medicine, University of Vermont, Burlington; 3 Department of Medicine, Division of Rheumatology, University of California at Los Angeles; and 4 Department of Medicine, Mount Sinai School of Medicine, New York, NY Treatment with the antimalarial drug hydroxychloroquine (HCQ) has been associated with reduced risk of thrombosis in the antiphospholipid (aPL) syndrome (APS) and, in an animal model of APS, with reduction of experimentally induced thrombosis. Recognition of β2-glycoprotein I (β2GPI) by aPL antibodies appears to play a major role in the disease process. We therefore used the techniques of ellipsometry and atomic force microscopy (AFM) to investigate whether HCQ directly affects the formation of aPL IgG–β2GPI complexes on phospholipid bilayers. HCQ, at concentrations of 1 µg/mL and greater, significantly reduced the binding of aPL-β2GPI complexes to phospholipid surfaces and THP-1 (human acute monocytic leukemia cell line) monocytes. The drug also reduced the binding of the individual proteins to bilayers. This HCQ-mediated reduction of binding was completely reversed when the HCQ-protein solutions were dialyzed against buffer. HCQ also caused modest, but statistically significant, reductions of clinical antiphospholipid assays. In conclusion, HCQ reduces the formation of aPL-β2GPI complexes to phospholipid bilayers and cells. This effect appears to be due to reversible interactions between HCQ and the proteins and may contribute to the observed reduction of thrombosis in human and experimental APS. These results support the possibility that HCQ, or analogous molecules, may offer novel nonanticoagulant therapeutic strategies for treating APS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Rand, X.-X. Wu, and A. Ashton Hydroxychloroquine Protects the Annexin A5 Anticoagulant Shield from Disruption by Antiphospholipid Antibodies Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 404 - 404. [Abstract]

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