血友病A中针对治疗性凝血因子VIII的同种抗体：血管性血友病因子在调节因子VIII免疫原性中的作用。
Alloantibodies to therapeutic factor VIII in hemophilia A: the role of von Willebrand factor in regulating factor VIII immunogenicity.
作者信息
Oldenburg Johannes, Lacroix-Desmazes Sébastien, Lillicrap David
机构信息
Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn, Germany.
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
出版信息
Haematologica. 2015 Feb;100(2):149-56. doi: 10.3324/haematol.2014.112821.
Abstract
The rising incidence of neutralizing antibodies (inhibitors) against therapeutic factor VIII prompted the conduct of studies to answer the question as to whether this rise is related to the introduction of recombinant factor VIII products. The present article summarizes current opinions and results of non-clinical and clinical studies on the immunogenic potential of recombinant compared to plasma-derived factor VIII concentrates. Numerous studies provided circumstantial evidence that von Willebrand factor, the natural chaperone protein present in plasma-derived factor VIII products, plays an important role in protecting exogenous factor VIII from uptake by antigen presenting cells and from recognition by immune effectors. However, the definite contribution of von Willebrand factor in reducing the inhibitor risk and in the achievement of immune tolerance is still under debate.
摘要
针对治疗性凝血因子VIII的中和抗体（抑制剂）发病率不断上升，促使人们开展研究，以解答这一上升是否与重组凝血因子VIII产品的引入有关。本文总结了关于重组凝血因子VIII浓缩物与血浆源性凝血因子VIII浓缩物免疫原性潜力的非临床和临床研究的当前观点及结果。大量研究提供了间接证据，表明血浆源性凝血因子VIII产品中存在的天然伴侣蛋白血管性血友病因子，在保护外源性凝血因子VIII不被抗原呈递细胞摄取以及不被免疫效应器识别方面发挥着重要作用。然而，血管性血友病因子在降低抑制剂风险和实现免疫耐受方面的确切作用仍存在争议。
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