Sawamoto Y, Shima M, Tanaka I, Nakai H, Kamisue S, Scandella D, Yoshioka A
Department of Pediatrics, Nara Medical College, Japan.
Int J Hematol. 1997 Feb;65(2):151-8. doi: 10.1016/s0925-5710(96)00555-5.
Anti-factor VIII (FVIII) inhibitor alloantibodies from 11 patients with hemophilia A, along with five anti-FVIII neutralizing monoclonal antibodies, were examined for differences in their reactivities with the A2 and C2 domains of human and porcine FVIII. None of the patients had been previously treated with porcine FVIII. Six inhibitors which specifically recognized the human FVIII C2 domain bound to both the 76-kDa porcine FVIII light chain and its 69-kDa proteolyzed fragments, showing cross-reactivity against porcine FVIII between 33 and 100%. Two A2-specific inhibitors did not react with porcine FVIII. The cross-reactivity was low (0-0.5%). The inhibitors recognizing both C2 and A2 reacted with the 76- and 69-kDa bands of porcine FVIII light chain, with cross-reactivity of between 11 and 33%. Monoclonal antibodies recognizing A1 (C-5) and A2 (JR8) did not react with the porcine FVIII. No anti-porcine FVIII neutralizing activity was detected in these antibodies. Monoclonal antibodies to the amino-terminal portion of A3 (NMC-VIII/10 and C-2) poorly reacted with the 76-kDa band, the cross-reactivities being 0 and 0.5%, respectively. NMC-VIII/5 recognizing C2 which competes with the C2-specific inhibitor, reacted with both the 76- and 69-kDa fragments showing cross-reactivity of 13%. These findings suggest that porcine A2 is antigenically different from human A2. The A2-specific inhibitor is a useful indicator for therapy with porcine FVIII.
对11例甲型血友病患者的抗凝血因子VIII（FVIII）抑制性同种抗体以及5种抗FVIII中和单克隆抗体，检测它们与人源和猪源FVIII的A2和C2结构域反应性的差异。这些患者之前均未接受过猪源FVIII治疗。6种特异性识别人类FVIII C2结构域的抑制剂与76 kDa猪源FVIII轻链及其69 kDa蛋白水解片段均结合，显示出对猪源FVIII 33%至100%的交叉反应性。两种A2特异性抑制剂不与猪源FVIII反应。交叉反应性较低（0 - 0.5%）。同时识别C2和A2的抑制剂与猪源FVIII轻链的76 kDa和69 kDa条带反应，交叉反应性在11%至33%之间。识别A1（C - 5）和A2（JR8）的单克隆抗体不与猪源FVIII反应。在这些抗体中未检测到抗猪源FVIII中和活性。针对A3氨基末端部分的单克隆抗体（NMC - VIII/10和C - 2）与76 kDa条带反应较弱，交叉反应性分别为0和0.5%。识别C2且与C2特异性抑制剂竞争的NMC - VIII/5与76 kDa和69 kDa片段均反应，交叉反应性为13%。这些发现表明猪源A2在抗原性上与人源A2不同。A2特异性抑制剂是猪源FVIII治疗的有用指标。
