Novel Hydroxychloroquine S-Isomer Dissociates Antiphospholipid Immune Complexes in Treatment of Antiphospholipid Syndrome

Background: Antiphospholipid syndrome (APS) is an autoimmune disorder with increased risk for thrombosis and pregnancy losses. There is no current consensus concerning the efficacy of this treatment in the secondary prevention of thrombotic events in primary APS. Hydroxychloroquine has recently demonstrated its efficacy and benefits in the several in vitro experimental and animal model data.Methods: In this study, the therapeutic effects of hydroxychloroquine (HCQ) analogs were evaluated under pathological conditions in vitro and ex vivo. We will focus on whether HCQ and its analogs can better prevent APS-induced cardiovascular thrombosis and are able to control antiphospholipid syndrome. In order to understand the pathophysiology of thrombogenesis and thrombus resolution, animal models are necessary.Findings: Our result determined that S- HCQ can better bind to the joint area of β2-Glycoprotein I to interfere its function than R-HCQ by molecular ducking analysis. The phenomenon was further proved by dot blot and ELISA, which showed S-HCQ can better inhibit the complex formation of β2-Glycoprotein I and anti-β2-Glycoprotein I than Rac-HCQ and R-HCQ in vitro.Interpretation: In this study, the therapeutic effects of hydroxychloroquine (HCQ) analogs were evaluated under pathological conditions in APS animal model. Mouse models of venous thrombosis contribute to our understanding of the initiation, propagation, and resolution of venous thrombus, as well as allow for the evaluation of new pharmaceutical approaches to prophylaxis and treatment of deep vein thrombosis.S-form hydroxychloroquine (HCQ) as an effective drug for antiphospholipid syndrome.Funding Information: This current study was backed by the National Science Council of Taiwan: Chi-Tai Yeh (MOST 111-2314-B-038-139 -). This research was backed by a grant from the National Taiwan University Hospital-Taipei Medical University Joint Research Program (NTUH-TMU Joint Research Program) offered to Chi-Tai Yeh (111-TMU303).Declaration of Interests: The authors stated they have not any potential financial competing interests that could in any way to gain or losing financially in publication of this manuscript now or the future. Ethics Approval Statement: All APS animal studies were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee (Institutional Animal Care and Use Committee, Taipei Medical University, Taipei, Taiwan, protocol approval number: LAC-2021-0629) , and all experiments complied with guidelines provided in The National Academies of Science, Engineering and Medicine Guide for the Care and Use 651 of Laboratory Animals.