Medical Research Center, Southwestern Hospital, The Third Military Medical University, Chongqing 400038, PR China.
Int Immunopharmacol. 2011 Jan;11(1):136-40. doi: 10.1016/j.intimp.2010.10.018. Epub 2010 Nov 13.
Anti-beta (2)-glycoprotein I (anti-β2-GP1) is one of the important pathogenesis factors responsible for thrombosis formation in patients with antiphospholipid syndrome (APS). Administration of intravenous immunoglobulin (IVIg) is a common method used to inhibit the abnormal antibody levels and decrease the mortality of APS in emergency situations. We hypothesize that the Fc fragment of IgG is the molecular structure responsible for these effects. The present study investigates the beneficial effects of both recombinant and natural human Fc fragments of heterogeneous IgG against human anti-β2-GP1 antibodies in mouse models with APS. Results showed that both recombinant and natural human Fc fragments moderately but significantly decreased the levels of serum anti-β2-GP1 antibodies and had anti-coagulation effects in human β2-GP1-immunized mice. Furthermore, both recombinant and natural human Fc fragments inhibited thrombosis formation and decreased mortality in mouse models infused intravenously with human anti-β2GP1 antibodies from patients with APS. Findings suggest that the Fc fragment might be one of the active structural units of heterogeneous IgG. Thus, recombinant human Fc fragment administration may be a useful treatment for individuals with APS.
抗β2-糖蛋白 I（anti-β2-GP1）是抗磷脂综合征（APS）患者血栓形成的重要发病机制因素之一。静脉注射免疫球蛋白（IVIg）是一种常见的方法，用于抑制异常抗体水平并降低 APS 患者的死亡率。我们假设 IgG 的 Fc 片段是负责这些效应的分子结构。本研究调查了重组和天然人异源 IgG 的 Fc 片段对 APS 小鼠模型中人类抗β2-GP1 抗体的有益作用。结果表明，重组和天然人 Fc 片段均能适度但显著降低血清抗β2-GP1 抗体水平，并在人β2-GP1 免疫小鼠中具有抗凝作用。此外，重组和天然人 Fc 片段均能抑制静脉内输注来自 APS 患者的人抗β2-GP1 抗体的小鼠模型中的血栓形成并降低死亡率。研究结果表明，Fc 片段可能是异源 IgG 的一个活性结构单位。因此，重组人 Fc 片段的给药可能是 APS 患者的一种有效治疗方法。
