A non-complement-fixing antibody to β2 glycoprotein I as a novel therapy for antiphospholipid syndrome
A non-complement-fixing antibody to β2 glycoprotein I as a novel therapy for antiphospholipid syndrome
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DOI：
10.1182/blood-2013-11-537704
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发表时间：
2014-05-29
期刊：
影响因子：
20.3
通讯作者：
Tedesco, Francesco
中科院分区：
文献类型：
--
作者：
Agostinis, Chiara;Durigutto, Paolo;Tedesco, Francesco
从人噬菌体展示文库中分离出识别人和其他物种的β 2-糖蛋白1（β 2GPI）的单链可变片段（scFv），并将其改造为含有IgG 1铰链-CH 2-CH 3结构域。scFv-Fc针对β 2GPI结构域I诱导的血栓形成和胎儿丢失，从而模拟来自抗磷脂综合征（APS）患者的抗体的作用。补体参与抗β 2GPI scFv-Fc的生物学效应，如其促进体外和体内补体沉积的能力以及在C6缺陷大鼠中诱导血管血栓形成和在C5缺失小鼠中诱导胎儿丢失的失败所证明的。补体的关键作用也得到CH 2缺失的scFv-Fc不能引起血管闭塞和妊娠失败的支持。该抗体防止来自APS患者的抗β 2GPI抗体的病理作用，并取代β 2GPI结合的患者抗体。CH 2缺失抗体代表了一种创新方法，可能用于治疗标准治疗难治性APS患者。
A single-chain fragment variable(scFv) recognizing beta 2-glycoprotein 1 (beta 2GPI) from humans and other species was isolated from a human phage display library and engineered to contain an IgG1 hinge-CH2-CH3 domain. The scFv-Fc directed against beta 2GPI domain I-induced thrombosis and fetal loss, thus mimicking the effect of antibodies from patients with antiphospholipid syndrome (APS). Complement is involved in the biological effect of anti-beta 2GPI scFv-Fc, as demonstrated by its ability to promote in vitro and in vivo complement deposition and the failure to induce vascular thrombosis in C6-deficient rats and fetal loss in C5-depletedmice. A critical role for complement was also supported by the inability of the CH2-deleted scFv-Fc to cause vessel occlusion and pregnancy failure. This antibody prevented the pathological effects of anti-beta 2GPI antibodies from APS patients and displaced beta 2GPI-bound patient antibodies. The CH2-deleted antibody represents an innovative approach potentially useful to treat APS patients refractory to standard therapy.