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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.
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Submitted March 10, 2008
Accepted June 3, 2008
Hydroxychloroquine directly reduces the binding of antiphospholipid antibody  2-glycoprotein I complexes to phospholipid bilayers
Jacob H. Rand*, Xiao-Xuan Wu, Anthony S Quinn, Pojen P Chen, James J Hathcock, and Douglas J Taatjes
Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, United States
Department of Pathology and Microscopy Imaging Center, College of Medicine, University of Vermont, Burlington, VT, United States
Department of Medicine, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, United States
Department of Medicine, Mount Sinai School of Medicine, New York, NY, United States
* Corresponding author; email: jrand{at}montefiore.org.
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  2-glycoprotein I (2GPI) 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-2GPI complexes on phospholipid bilayers.
HCQ, at concentrations of 1 µg/mL and greater, significantly reduced the binding of aPL-2GPI complexes to phospholipid surfaces and THP-1 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-2GPI 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.
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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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