Lubin I M, Healey J F, Scandella D, Runge M S, Lollar P
Department of Medicine, Emory University, Atlanta, Georgia 30322.
J Biol Chem. 1994 Mar 25;269(12):8639-41.
The A2 and C2 domains of human blood coagulation factor VIII (fVIII) contain the epitopes targeted by most inhibitory allo- and autoantibodies. Human inhibitors usually display limited or no reaction with porcine fVIII. We constructed an active, recombinant hybrid human/porcine fVIII molecule by replacing the putative human fVIII A2 domain epitope with the homologous porcine sequence. The hybrid retained full activity in the presence of antibodies with specificity restricted to the human A2 epitope. In contrast, the hybrid was neutralized by an anti-C2 antibody. These findings provide a basis for fine epitope mapping and for therapy of the inhibitor patient.
人凝血因子VIII（fVIII）的A2和C2结构域包含大多数抑制性同种异体和自身抗体靶向的表位。人抑制剂通常与猪fVIII反应有限或无反应。我们通过用同源猪序列替换推定的人fVIII A2结构域表位构建了一种活性重组人/猪杂交fVIII分子。在存在特异性限于人A2表位的抗体时，该杂交分子保留了全部活性。相比之下，该杂交分子被一种抗C2抗体中和。这些发现为精细表位定位和抑制剂患者的治疗提供了基础。
