Giannakopoulos Bill, Passam Freda, Rahgozar Soheila, Krilis Steven A
Department of Immunology, Allergy and Infectious Diseases, 2 South St, Sydney, University of New South Wales 2217, St George Hospital, Australia.
Blood. 2007 Jan 15;109(2):422-30. doi: 10.1182/blood-2006-04-001206. Epub 2006 Sep 19.
The antiphospholipid syndrome (APS) is an important cause of acquired thrombophilia. It is characterized by the core clinical manifestations of thrombosis, either venous or arterial, and in women it can also be associated with recurrent fetal loss. The detection of persistently elevated levels of antiphospholipid antibodies (aPL Abs) is a requisite laboratory feature for the diagnosis to be made. The dominant antigenic targets in APS are beta 2-glycoprotein I (beta2-GPI) and prothrombin. There is an accumulating body of experimental evidence that suggests that specific subgroups of aPL Abs may directly contribute to disease pathogenesis. This review critically examines the experimental evidence underlying the various propositions made to explain how these antibodies may predispose to disease in humans. Furthermore, it also examines the evidence relating to the immunologic mechanisms that may contribute to the breakage of peripheral tolerance in this disorder. Delineating the strengths and limitations of the experimental evidence accumulated thus far will hopefully stimulate further experimentation toward achieving the ultimate goal of precisely defining the dominant pathogenic mechanisms operational in APS. This may pave the way for the development of improved therapies.
抗磷脂综合征（APS）是获得性血栓形成倾向的一个重要原因。其核心临床表现为静脉或动脉血栓形成，在女性中还可伴有反复流产。检测到抗磷脂抗体（aPL Abs）持续升高是作出诊断所需的实验室特征。APS中的主要抗原靶点是β2糖蛋白I（β2-GPI）和凝血酶原。越来越多的实验证据表明，aPL Abs的特定亚组可能直接促成疾病的发病机制。本综述批判性地审视了各种观点背后的实验证据，这些观点旨在解释这些抗体如何使人易患疾病。此外，还审视了与免疫机制相关的证据，这些机制可能导致该疾病外周耐受性的破坏。阐明迄今为止积累的实验证据的优势和局限性，有望激发进一步的实验，以实现精确界定APS中主要致病机制这一最终目标。这可能为开发改进的治疗方法铺平道路。
