Hydroxychloroquine directly reduces the bindin of antiphospholipid antibody-β2-glycoprotein I complexes to phospholipid bilayers

Jacob H. Rand, Xiao Xuan Wu, Anthony S. Quinn, Pojen P. Chen, James J. Hathcock, Douglas J. Taatjes

Research output: Contribution to journalArticlepeer-review

179 Scopus citations

Abstract

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 β-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.

Original languageEnglish
Pages (from-to)1687-1695
Number of pages9
JournalBlood
Volume112
Issue number5
DOIs
StatePublished - 1 Sep 2008
Externally publishedYes

Fingerprint

Dive into the research topics of 'Hydroxychloroquine directly reduces the bindin of antiphospholipid antibody-β2-glycoprotein I complexes to phospholipid bilayers'. Together they form a unique fingerprint.

Cite this