Centre for Rheumatology Research, University College London, Division of Medicine, London, UK.
Expert Opin Ther Targets. 2010 Dec;14(12):1291-9. doi: 10.1517/14728222.2010.524207. Epub 2010 Sep 28.
The antiphospholipid syndrome (APS) is an autoimmune condition whereby pathogenic antiphospholipid antibodies (aPL) cause vascular thrombosis and/or recurrent miscarriage, and carries a high burden of morbidity and mortality. Currently the only proven treatment is long-term anticoagulation, which is not effective in all patients and carries risk of haemorrhage.
Novel therapeutic targets that are currently being explored for APS in order to address the unmet needs of better, safer and ideally targeted therapy. These include B cell depletion, new-generation anticoagulants, interfering with aPL cell-mediated activation of endothelial cells and platelets both at the cell surface level and intracellularly, targeting components of the complement system and the novel concept of using decoy peptides to target only the pathogenic sub-population of aPL.
An overview of the potential targets and rationale underpinning them.
Though current options remain limited for the treatment of APS, the future holds much promise with the identification of multiple targets, many of which are currently being explored. The challenge will be to undertake carefully designed prospective multi-centre trials to generate the evidence necessary to support integration of such candidates into clinical practice.
抗磷脂综合征(APS)是一种自身免疫性疾病,致病性抗磷脂抗体(aPL)导致血管血栓形成和/或复发性流产,并伴有高发病率和死亡率。目前唯一被证实的治疗方法是长期抗凝治疗,但并非对所有患者都有效,而且有出血风险。
目前正在探索用于 APS 的新型治疗靶点,以满足更好、更安全且理想靶向治疗的未满足需求。这些包括 B 细胞耗竭、新一代抗凝剂、干扰 aPL 细胞介导的内皮细胞和血小板的激活,包括细胞表面和细胞内水平、靶向补体系统的成分以及使用诱饵肽靶向仅致病性 aPL 亚群的新概念。
对潜在靶点及其基础原理的概述。
尽管目前治疗 APS 的选择仍然有限,但随着多个靶点的确定,未来充满希望,其中许多靶点目前正在探索中。挑战将是进行精心设计的前瞻性多中心试验,以产生必要的证据,支持将这些候选药物整合到临床实践中。