Scandella D
Holland Laboratory, American Red Cross, Rockville, Md 20879, USA.
Vox Sang. 1996;70 Suppl 1:9-14.
Recombinant polypeptides derived from coagulation factor VIII (fVIII) have been used to determine the epitopes and characteristics of human pathologic anti-fVIII antibodies. The results of immunoprecipitation assays indicate that 70% of patient plasmas contain antibodies to the A2 as well as the C2 domains of the fVIII protein. The same polypeptides were used for inhibitor neutralization assays to demonstrate that about 60% of plasmas contain 2 or 3 different antibodies which collectively make up the inhibitor titer. The results of neutralization assays indicate that there is a third important inhibitor epitope within the light chain outside C2. Anti-A2 antibodies prevent normal function of the factor Xase complex of the intrinsic pathway of blood coagulation. Anti-C2 antibodies prevent the binding of fVIII to phospholipid and to von Willebrand factor, both of which are important for normal fVIII function.
源自凝血因子VIII（fVIII）的重组多肽已被用于确定人类病理性抗fVIII抗体的表位和特性。免疫沉淀试验结果表明，70%的患者血浆含有针对fVIII蛋白A2结构域以及C2结构域的抗体。相同的多肽被用于抑制剂中和试验，以证明约60%的血浆含有2种或3种不同的抗体，这些抗体共同构成抑制剂滴度。中和试验结果表明，在C2结构域外的轻链内存在第三个重要的抑制剂表位。抗A2抗体可阻止内源性凝血途径中因子X酶复合物的正常功能。抗C2抗体可阻止fVIII与磷脂以及血管性血友病因子结合，而这两者对fVIII的正常功能都很重要。
