Proteomics Core, COBRE Center for Cancer Research Development, Rhode Island Hospital, Providence, RI, USA.
Electrophoresis. 2009 Oct;30(20):3636-46. doi: 10.1002/elps.200900270.
Proteomic methods were used to identify the levels of impurities in three commercial plasma-derived clotting factor VIII-von Willebrand factor (FVIII/VWF) concentrates. In all three concentrates, significant amounts of other plasma proteins were found. In Octanate and Haemoctin, two concentrates developed in the 1990s, the major impurities identified were inter-alpha inhibitor proteins, fibrinogen and fibronectin. These two concentrates were also found to contain additional components such as clotting factor II (prothrombin) that are known activators of FVIII. In Wilate, a recently developed FVIII/VWF concentrate, the amount of these impurities was significantly reduced. Batch-to-batch variations and differences between three investigated products were detected using iTRAQ, an isotope labeling technique for comparative MS, demonstrating the potential value of this technique for quality control analysis. The importance of thorough proteomic investigations of therapeutic FVIII/VWF preparations from human plasma is also discussed.
采用蛋白质组学方法鉴定了三种商业来源的血浆凝血因子 VIII-血管性血友病因子（FVIII/VWF）浓缩物中的杂质水平。在这三种浓缩物中，均发现了大量其他血浆蛋白。在 20 世纪 90 年代开发的两种浓缩物Octanate 和 Haemoctin 中，鉴定出的主要杂质是抗凝血酶原蛋白、纤维蛋白原和纤维连接蛋白。这两种浓缩物还含有其他成分，如凝血因子 II（凝血酶原），已知其是 FVIII 的激活剂。在最近开发的 FVIII/VWF 浓缩物 Wilate 中，这些杂质的含量显著降低。使用 iTRAQ（一种用于比较 MS 的同位素标记技术）检测到批次间差异和三种研究产品之间的差异，表明该技术在质量控制分析方面具有潜在价值。还讨论了对人血浆来源的治疗性 FVIII/VWF 制剂进行全面蛋白质组学研究的重要性。
