Zimring James C, Cadwell Chantel M, Chadwick Traci E, Spitalnik Steven L, Schirmer David A, Wu Tao, Parkos Charles A, Hillyer Christopher D
Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
Blood. 2007 Sep 15;110(6):2201-8. doi: 10.1182/blood-2007-04-083097. Epub 2007 Jun 14.
Transfusion of crossmatch-incompatible red blood cells (RBCs) can result in antibody-mediated hemolysis. However, in some patients, crossmatch-incompatible RBCs lose the incompatible antigen from their surface, and then circulate normally ("antigen loss"). Although antigen loss has been reported in the settings of autoimmune hemolytic anemia and transfusion of crossmatch-incompatible RBCs, mechanistic understanding of this phenomenon is limited. Using an in vivo murine model of antigen loss, we report that, unlike polyclonal antisera, monoclonal antibodies did not induce antigen loss. However, the combination of 2 monoclonal antibodies that recognized separate epitopes on the same antigen induced antigen loss. This was not due to an increased number of Fc domains bound to the cell surface, because antigen loss still occurred when combining intact monoclonal IgG and F(ab')2 fragments recognizing different epitopes. Together, these data lead to the hypothesis that antigen-antibody crosslinking is required for nonhemolytic antigen loss to occur.
输注交叉配血不相容的红细胞（RBC）可导致抗体介导的溶血。然而，在一些患者中，交叉配血不相容的RBC会从其表面丢失不相容抗原，然后正常循环（“抗原丢失”）。尽管在自身免疫性溶血性贫血和输注交叉配血不相容RBC的情况下已报道了抗原丢失，但对这一现象的机制理解有限。使用抗原丢失的体内小鼠模型，我们报告，与多克隆抗血清不同，单克隆抗体不会诱导抗原丢失。然而，识别同一抗原上不同表位的两种单克隆抗体的组合可诱导抗原丢失。这并非由于与细胞表面结合的Fc结构域数量增加，因为当完整的单克隆IgG与识别不同表位的F(ab')2片段组合时，抗原丢失仍会发生。总之，这些数据得出一个假设，即非溶血性抗原丢失的发生需要抗原-抗体交联。
