Anti-factor VIII inhibitor alloantibodies recognizing the A2 domain in the human factor VIII heavy chain poorly bind to porcine factor VIII.
Anti-factor VIII inhibitor alloantibodies recognizing the A2 domain in the human factor VIII heavy chain poorly bind to porcine factor VIII.
复制标题
识别人因子 VIII 重链中 A2 结构域的抗因子 VIII 抑制剂同种抗体与猪因子 VIII 的结合较差。
DOI：
10.1016/s0925-5710(96)00555-5
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发表时间：
1997
影响因子：
2.1
通讯作者：
A. Yoshioka
中科院分区：
文献类型：
--
作者：
Y. Sawamoto;M. Shima;I. Tanaka;H. Nakai;S. Kamisue;D. Scandella;A. Yoshioka
研究了11例A型血友病患者的抗因子VIII （FVIII）抑制剂同种抗体，以及5种抗FVIII中和性单克隆抗体，检测了它们与人和猪FVIII A2和C2结构域的反应性差异。这些患者以前均未接受过猪流感病毒治疗。6种抑制剂特异性识别人FVIII C2结构域结合到76-kDa的猪FVIII轻链及其69-kDa的蛋白水解片段，对猪FVIII表现出33%至100%的交叉反应性。两种a2特异性抑制剂与猪FVIII没有反应。交叉反应性低（0-0.5%）。识别C2和A2的抑制剂与猪FVIII轻链的76和69 kda带发生反应，交叉反应活性在11%到33%之间。识别A1 （C-5）和A2 （JR8）的单克隆抗体与猪FVIII无反应。这些抗体未检测到抗猪FVIII的中和活性。A3氨基末端的单克隆抗体（NMC-VIII/10和C-2）与76-kDa带反应较差，交叉反应度分别为0和0.5%。NMC-VIII/5识别与C2特异性抑制剂竞争的C2，与76- kda和69-kDa片段均发生反应，交叉反应性为13%。这些发现表明猪A2在抗原性上不同于人A2。a2特异性抑制剂是猪FVIII治疗的有用指标。
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.